Journal articles: 'Biomarkers of neurodegenerative disease'

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Raghunathan, Rekha, Kathleen Turajane, and Li Chin Wong. "Biomarkers in Neurodegenerative Diseases: Proteomics Spotlight on ALS and Parkinson’s Disease." International Journal of Molecular Sciences 23, no. 16 (August 18, 2022): 9299. http://dx.doi.org/10.3390/ijms23169299.

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Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) are both characterized by pathogenic protein aggregates that correlate with the progressive degeneration of neurons and the loss of behavioral functions. Both diseases lack biomarkers for diagnosis and treatment efficacy. Proteomics is an unbiased quantitative tool capable of the high throughput quantitation of thousands of proteins from minimal sample volumes. We review recent proteomic studies in human tissues, plasma, cerebrospinal fluid (CSF), and exosomes in ALS and PD that identify proteins with potential utility as biomarkers. Further, we review disease-related post-translational modifications in key proteins TDP43 in ALS and α-synuclein in PD studies, which may serve as biomarkers. We compare relative and absolute quantitative proteomic approaches in key biomarker studies in ALS and PD and discuss recent technological advancements which may identify suitable biomarkers for the early-diagnosis treatment efficacy of these diseases.

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Martínez-Iglesias, Olaia, Vinogran Naidoo, Natalia Cacabelos, and Ramón Cacabelos. "Epigenetic Biomarkers as Diagnostic Tools for Neurodegenerative Disorders." International Journal of Molecular Sciences 23, no. 1 (December 21, 2021): 13. http://dx.doi.org/10.3390/ijms23010013.

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Epigenetics is the study of heritable changes in gene expression that occur without alterations to the DNA sequence, linking the genome to its surroundings. The accumulation of epigenetic alterations over the lifespan may contribute to neurodegeneration. The aim of the present study was to identify epigenetic biomarkers for improving diagnostic efficacy in patients with neurodegenerative diseases. We analyzed global DNA methylation, chromatin remodeling/histone modifications, sirtuin (SIRT) expression and activity, and the expression of several important neurodegeneration-related genes. DNA methylation, SIRT expression and activity and neuregulin 1 (NRG1), microtubule-associated protein tau (MAPT) and brain-derived neurotrophic factor (BDNF) expression were reduced in buffy coat samples from patients with neurodegenerative disorders. Our data suggest that these epigenetic biomarkers may be useful in clinical practical for the diagnosis, surveillance, and prognosis of disease activity in patients with neurodegenerative diseases.

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Miller, Elżbieta, Agnieszka Morel, Luciano Saso, and Joanna Saluk. "Isoprostanes and Neuroprostanes as Biomarkers of Oxidative Stress in Neurodegenerative Diseases." Oxidative Medicine and Cellular Longevity 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/572491.

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Accumulating data shows that oxidative stress plays a crucial role in neurodegenerative disorders. The literature data indicate thatin vivoor postmortem cerebrospinal fluid and brain tissue levels of F2-isoprostanes (F2-IsoPs) especially F4-neuroprotanes (F4-NPs) are significantly increased in some neurodegenerative diseases: multiple sclerosis, Alzheimer's disease, Huntington's disease, and Creutzfeldt-Jakob disease. Central nervous system is the most metabolically active organ of the body characterized by high requirement for oxygen and relatively low antioxidative activity, what makes neurons and glia highly susceptible to destruction by reactive oxygen/nitrogen species and neurodegeneration. The discovery of F2-IsoPs and F4-NPs as markers of lipid peroxidation caused by the free radicals has opened up new areas of investigation regarding the role of oxidative stress in the pathogenesis of human neurodegenerative diseases. This review focuses on the relationship between F2-IsoPs and F4-NPs as biomarkers of oxidative stress and neurodegenerative diseases. We summarize the knowledge of these novel biomarkers of oxidative stress and the advantages of monitoring their formation to better define the involvement of oxidative stress in neurological diseases.

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Azevedo, Rita, Chloé Jacquemin, Nicolas Villain, François Fenaille, Foudil Lamari, and François Becher. "Mass Spectrometry for Neurobiomarker Discovery: The Relevance of Post-Translational Modifications." Cells 11, no. 8 (April 9, 2022): 1279. http://dx.doi.org/10.3390/cells11081279.

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Neurodegenerative diseases are incurable, heterogeneous, and age-dependent disorders that challenge modern medicine. A deeper understanding of the pathogenesis underlying neurodegenerative diseases is necessary to solve the unmet need for new diagnostic biomarkers and disease-modifying therapy and reduce these diseases’ burden. Specifically, post-translational modifications (PTMs) play a significant role in neurodegeneration. Due to its proximity to the brain parenchyma, cerebrospinal fluid (CSF) has long been used as an indirect way to measure changes in the brain. Mass spectrometry (MS) analysis in neurodegenerative diseases focusing on PTMs and in the context of biomarker discovery has improved and opened venues for analyzing more complex matrices such as brain tissue and blood. Notably, phosphorylated tau protein, truncated α-synuclein, APP and TDP-43, and many other modifications were extensively characterized by MS. Great potential is underlying specific pathological PTM-signatures for clinical application. This review focuses on PTM-modified proteins involved in neurodegenerative diseases and highlights the most important and recent breakthroughs in MS-based biomarker discovery.

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Lemieszewska, Marta, Agnieszka Zabłocka, and Joanna Rymaszewska. "Parkinson’s disease: Etiopathogenesis, molecular basis and potential treatment opportunities." Postępy Higieny i Medycyny Doświadczalnej 73 (May 15, 2019): 256–68. http://dx.doi.org/10.5604/01.3001.0013.2021.

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Neurodegenerative diseases affect the life quality and lifespan of aging populations. Among all forms of neurodegenerative diseases, Parkinson’s disease (PD) has a massive impact on the elderly. Oxidative stress and mitochondrial dysfunction are the main causes of neurodegeneration and progression of PD. Oxidative stress, which plays a vital role in the pathophysiology of PD, is related to the dysfunction of cellular antioxidant mechanisms as a result of enhanced production of reactive oxygen species. A large number of studies have utilized oxidative stress biomarkers to investigate the severity of neurodegeneration and medications are available, but these only treat the symptoms. Extensive studies scientifically validated the beneficial effect of natural products against neurodegenerative diseases, using suitable animal models. The review focuses on the role of oxidative stress in the pathogenesis of Parkinson’s disease and the protective potential of natural products against neurodegeneration.

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Harrington, Karra D., Andrew J. Aschenbrenner, Paul Maruff, Colin L. Masters, Anne M. Fagan, Tammie L. S. Benzinger, Brian A. Gordon, Carlos Cruchaga, John C. Morris, and Jason Hassenstab. "Undetected Neurodegenerative Disease Biases Estimates of Cognitive Change in Older Adults." Psychological Science 32, no. 6 (May 27, 2021): 849–60. http://dx.doi.org/10.1177/0956797620985518.

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Neurodegenerative disease is highly prevalent among older adults and, if undetected, may obscure estimates of cognitive change among aging samples. Our aim in this study was to determine the nature and magnitude of cognitive change in the absence of common neuropathologic markers of neurodegenerative disease. Cognitively normal older adults (ages 65–89 years, N = 199) were classified as normal or abnormal using neuroimaging and cerebrospinal-fluid biomarkers of β-amyloid, tau, and neurodegeneration. When cognitive change was modeled without accounting for biomarker status, significant decline was evident for semantic memory, processing speed, and working memory. However, after adjusting for biomarker status, we found that the rate of change was attenuated and that the biomarker-normal group demonstrated no decline for any cognitive domain. These results indicate that estimates of cognitive change in otherwise healthy older adults will be biased toward decline when the presence of early neurodegenerative disease is not accounted for.

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Gasecka, Aleksandra, Dominika Siwik, Magdalena Gajewska, Miłosz J. Jaguszewski, Tomasz Mazurek, Krzysztof J. Filipiak, Marek Postuła, and Ceren Eyileten. "Early Biomarkers of Neurodegenerative and Neurovascular Disorders in Diabetes." Journal of Clinical Medicine 9, no. 9 (August 30, 2020): 2807. http://dx.doi.org/10.3390/jcm9092807.

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Diabetes mellitus (DM) is a common disease worldwide. There is a strong association between DM and neurovascular and neurodegenerative disorders. The first group mainly consists of diabetic retinopathy, diabetic neuropathy and stroke, whereas, the second group includes Alzheimer’s disease, Parkinson’s disease, mild cognitive impairment and dementia. The aforementioned diseases have a common pathophysiological background including insulin resistance, oxidative stress, atherosclerosis and vascular injury. The increasing prevalence of neurovascular and neurodegenerative disorders among diabetic patients has resulted in an urgent need to develop biomarkers for their prediction and/or early detection. The aim of this review is to present the potential application of the most promising biomarkers of diabetes-related neurodegenerative and neurovascular disorders, including amylin, β-amyloid, C-reactive protein (CRP), dopamine, gamma-glutamyl transferase (GGT), glycogen synthase kinase 3β, homocysteine, microRNAs (mi-RNAs), paraoxonase 1, phosphoinositide 3-kinases, tau protein and various growth factors. The most clinically promising biomarkers of neurovascular and neurodegenerative complications in DM are hsCRP, GGT, homocysteine and miRNAs. However, all biomarkers discussed in this review could become a part of the potential multi-biomarker screening panel for diabetic patients at risk of neurovascular and neurodegenerative complications.

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Maciejczyk, Mateusz, Anna Zalewska, and Karolina Gerreth. "Salivary Redox Biomarkers in Selected Neurodegenerative Diseases." Journal of Clinical Medicine 9, no. 2 (February 12, 2020): 497. http://dx.doi.org/10.3390/jcm9020497.

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Neurodegenerative diseases (NDDs), such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, are disorders, which cause irreversible and progressive deterioration of the central nervous system. The pathophysiology of NDDs is still not fully explained; nevertheless, oxidative stress is considered as a critical mediator of cerebral degeneration, brain inflammation, as well as neuronal apoptosis. Therefore, it is not surprising that redox biomarkers are increasingly used in the diagnosis of neurodegenerative diseases. As saliva is a very easy to obtain bioliquid, it seems promising to use this biomaterial in the diagnosis of NDDs. Saliva collection is easy, cheap, stress-free, and non-infectious, and it does not require the help of a specialised medical personnel. Additionally, the concentrations of many salivary redox biomarkers correlate with their content in blood serum as well as the degree of disease progression, which makes them non-invasive indicators of NDDs. This paper reviews the latest knowledge concerning the use of salivary redox biomarkers in the diagnosis and prognosis of selected neurodegenerative diseases.

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Betts, Matthew J., Evgeniya Kirilina, Maria C. G. Otaduy, Dimo Ivanov, Julio Acosta-Cabronero, Martina F. Callaghan, Christian Lambert, et al. "Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases." Brain 142, no. 9 (July 20, 2019): 2558–71. http://dx.doi.org/10.1093/brain/awz193.

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Abstract Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now provide an opportunity to quantify structural features of the locus coeruleus in vivo during disease progression. In combination with neuropathological biomarkers, in vivo locus coeruleus imaging could help to understand the contribution of locus coeruleus neurodegeneration to clinical and pathological manifestations in Alzheimer’s disease, atypical neurodegenerative dementias and Parkinson’s disease. Moreover, as the functional sensitivity of the noradrenergic system is likely to change with disease progression, in vivo measures of locus coeruleus integrity could provide new pathophysiological insights into cognitive and behavioural symptoms. Locus coeruleus imaging also holds the promise to stratify patients into clinical trials according to noradrenergic dysfunction. In this article, we present a consensus on how non-invasive in vivo assessment of locus coeruleus integrity can be used for clinical research in neurodegenerative diseases. We outline the next steps for in vivo, post-mortem and clinical studies that can lay the groundwork to evaluate the potential of locus coeruleus imaging as a biomarker for neurodegenerative diseases.

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Mollinari, Cristiana, Chiara De Dominicis, Leonardo Lupacchini, Luigi Sansone, Davide Caprini, Carlo Massimo Casciola, Ying Wang, et al. "Detection of Pathological Markers of Neurodegenerative Diseases following Microfluidic Direct Conversion of Patient Fibroblasts into Neurons." International Journal of Molecular Sciences 23, no. 4 (February 15, 2022): 2147. http://dx.doi.org/10.3390/ijms23042147.

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Neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are clinically diagnosed using neuropsychological and cognitive tests, expensive neuroimaging-based approaches (MRI and PET) and invasive and time-consuming lumbar puncture for cerebrospinal fluid (CSF) sample collection to detect biomarkers. Thus, a rapid, simple and cost-effective approach to more easily access fluids and tissues is in great need. Here, we exploit the chemical direct reprogramming of patient skin fibroblasts into neurons (chemically induced neurons, ciNs) as a novel strategy for the rapid detection of different pathological markers of neurodegenerative diseases. We found that FAD fibroblasts have a reduced efficiency of reprogramming, and converted ciNs show a less complex neuronal network. In addition, ciNs from patients show misfolded protein accumulation and mitochondria ultrastructural abnormalities, biomarkers commonly associated with neurodegeneration. Moreover, for the first time, we show that microfluidic technology, in combination with chemical reprogramming, enables on-chip examination of disease pathological processes and may have important applications in diagnosis. In conclusion, ciNs on microfluidic devices represent a small-scale, non-invasive and cost-effective high-throughput tool for protein misfolding disease diagnosis and may be useful for new biomarker discovery, disease mechanism studies and design of personalised therapies.

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Török, Nóra, Masaru Tanaka, and László Vécsei. "Searching for Peripheral Biomarkers in Neurodegenerative Diseases: The Tryptophan-Kynurenine Metabolic Pathway." International Journal of Molecular Sciences 21, no. 24 (December 8, 2020): 9338. http://dx.doi.org/10.3390/ijms21249338.

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Neurodegenerative diseases are multifactorial, initiated by a series of the causative complex which develops into a certain clinical picture. The pathogenesis and disease course vary from patient to patient. Thus, it should be likewise to the treatment. Peripheral biomarkers are to play a central role for tailoring a personalized therapeutic plan for patients who suffered from neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, among others. Nevertheless, the use of biomarkers in clinical practice is still underappreciated and data presented in biomarker research for clinical use is still uncompelling, compared to the abundant data available for drug research and development. So is the case with kynurenines (KYNs) and the kynurenine pathway (KP) enzymes, which have been associated with a wide range of diseases including cancer, autoimmune diseases, inflammatory diseases, neurologic diseases, and psychiatric disorders. This review article discusses current knowledge of KP alterations observed in the central nervous system as well as the periphery, its involvement in pathogenesis and disease progression, and emerging evidence of roles of microbiota in the gut-brain axis, searching for practical peripheral biomarkers which ensure personalized treatment plans for neurodegenerative diseases.

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Bălașa, Adrian Florian, Cristina Chircov, and Alexandru Mihai Grumezescu. "Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview." Biomedicines 8, no. 10 (October 15, 2020): 421. http://dx.doi.org/10.3390/biomedicines8100421.

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Neurodegeneration is a highly complex process which is associated with a variety of molecular mechanisms related to ageing. Among neurodegenerative disorders, Alzheimer’s disease (AD) is the most common, affecting more than 45 million individuals. The underlying mechanisms involve amyloid plaques and neurofibrillary tangles (NFTs) deposition, which will subsequently lead to oxidative stress, chronic neuroinflammation, neuron dysfunction, and neurodegeneration. The current diagnosis methods are still limited in regard to the possibility of the accurate and early detection of the diseases. Therefore, research has shifted towards the identification of novel biomarkers and matrices as biomarker sources, beyond amyloid-β and tau protein levels within the cerebrospinal fluid (CSF), that could improve AD diagnosis. In this context, the aim of this paper is to provide an overview of both conventional and novel biomarkers for AD found within body fluids, including CSF, blood, saliva, urine, tears, and olfactory fluids.

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Allegri, Ricardo Francisco. "Moving from neurodegenerative dementias, to cognitive proteinopathies, replacing “where” by “what”…" Dementia & Neuropsychologia 14, no. 3 (September 2020): 237–42. http://dx.doi.org/10.1590/1980-57642020dn14-030005.

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ABSTRACT. Neurodegenerative dementias have been described based on their phenotype, in relation to selective degeneration occurring in a particular neuroanatomical system. More recently however, the term proteinopathy has been introduced to describe diseases in which one or more altered proteins can be detected. Neurodegenerative diseases can be produced by more than one abnormal protein and each proteinopathy can determine different clinical phenotypes. Specific biomarkers have now been linked to certain molecular pathologies in live patients. In 2016, a new biomarker-based classification, currently only approved for research in Alzheimer’s disease, was introduced. It is based on the evaluation three biomarkers: amyloid (A) detected on amyloid-PET or amyloid- beta 42 assay in CSF; tau (T) measured in CSF as phosphorylated tau or on tau PET imaging; and neuronal injury/neurodegeneration (N), detected by total T-tau in CSF, FDG PET hypometabolism and on MRI brain scan. Results of clinical research using the ATN biomarkers at FLENI, a Neurological Institute in Buenos Aires, Argentina have, since 2011, contributed to ongoing efforts to move away from the concept of neurodegenerative dementias and more towards one of cognitive proteinopathies. Today, clinical diagnosis in dementia can only tell us “where” abnormal tissue is found but not “what” molecular mechanisms are involved.

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Henley, Susie MD, Gillian P. Bates, and Sarah J. Tabrizi. "Biomarkers for neurodegenerative diseases." Current Opinion in Neurology 18, no. 6 (December 2005): 698–705. http://dx.doi.org/10.1097/01.wco.0000186842.51129.cb.

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Hansson, Oskar. "Biomarkers for neurodegenerative diseases." Nature Medicine 27, no. 6 (June 2021): 954–63. http://dx.doi.org/10.1038/s41591-021-01382-x.

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Yusupov, F., and A. Yuldashev. "Biomarkers of Neurodegenerative Diseases." Bulletin of Science and Practice 7, no. 9 (September 15, 2021): 341–53. http://dx.doi.org/10.33619/2414-2948/70/30.

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The proportion of neurodegenerative diseases among all neurological disorders is growing year after year. This is explained by the duration of the latency period and the manifestation of signs after the death of about 40–60% of neurons. According to WHO forecasts, neurodegenerative diseases will be the biggest problem in the healthcare system of the XXI century. Among them, the most acute can be considered Alzheimer’s and Parkinson’s diseases. Specific biomarkers of neurodegenerative diseases (diseases: Alzheimer’s; Parkinson’s; Huntington’s) are discussed. Currently, the highest priority in neurology is the identification of specific biomarkers in the blood serum for each nosology. In medicine, less invasive, atraumatic methods are always encouraged, therefore, the detection of biomarkers in the blood has advantages over the detection in the cerebrospinal fluid, the production of which is more invasive. The review examines the biomarkers of Alzheimer’s, Parkinson’s and Huntington’s diseases.

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Ghosh, Arnab. "Biomarkers in Neurodegenerative Diseases." Biomedicines 10, no. 2 (January 20, 2022): 215. http://dx.doi.org/10.3390/biomedicines10020215.

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Frost, Shaun M., Yogesan Kanagasingam, and S. Lance Macaulay. "Ocular biomarkers for neurodegenerative and systemic disease." Medical Journal of Australia 201, no. 3 (August 2014): 128. http://dx.doi.org/10.5694/mja14.00924.

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Hudson, C. "Candidate Retinal Biomarkers in CNS Neurodegenerative Disease." Acta Ophthalmologica 93 (September 23, 2015): n/a. http://dx.doi.org/10.1111/j.1755-3768.2015.0245.

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Anderson, K. N., W. B. Overcast, J. R. Brosch, B. D. Graner, and M. C. Veronesi. "Prionopathies and Prionlike Protein Aberrations in Neurodegenerative Diseases." Neurographics 11, no. 2 (March 1, 2021): 127–48. http://dx.doi.org/10.3174/ng.2000035.

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Protein misfolding has been an area of intense research and is implicated in a number of neurodegenerative diseases. Key proteins in the brain lose their native ability to fold and instead assume abnormal conformations. Misfolded proteins cluster to form pathologic aggregates, which cause cellular dysfunction, neuronal death, and neurodegeneration. The prionopathies are best known among the neurodegenerative diseases for their ability to misfold, self-propagate, and infect other organisms. There is increasing evidence of a rationale for a prionlike mechanism of spread of other neurodegenerative diseases through a similar seeding mechanism. In this review, we detail the role of a key protein aberration known to the various prion diseases, including sporadic, variant, and iatrogenic Creutzfeldt-Jakob disease; variably protease-sensitive prionopathy; Gerstmann-Straussler-Scheinker disease; fatal familial insomnia; and kuru. We also discuss the clinical presentation, the available, and emerging imaging options for these diseases. In the second part of this review, we delineate how a prionlike seeding process may be driving the progression of other neurodegenerative diseases, including Parkinson disease, Alzheimer disease, and Huntington disease. A discussion of clinical presentation and imaging features of these example diseases follows to make a case for a common approach to developing imaging biomarkers and therapies of these diseases.Learning Objective: Upon completion of this article, one should be able to describe the various types of prion diseases, recognize and identify the common the neuro-imaging findings in prion diseases, describe seeding mechanism of prion disease, list the common amyloid PET tracers used for Alzheimer’s disease, and list common imaging biomarkers in neurodegenerative diseases.

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Spitzer, Philipp, Hans Wolfgang Klafki, Kaj Blennow, Luc Buée, Hermann Esselmann, Sanna-Kaisa Herruka, Connie Jimenez, et al. "cNEUPRO: Novel Biomarkers for Neurodegenerative Diseases." International Journal of Alzheimer's Disease 2010 (September 19, 2010): 1–12. http://dx.doi.org/10.4061/2010/548145.

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“clinical NEUroPROteomics of neurodegenerative diseases” (cNEUPRO) is a Specific Targeted Research Project (STREP) within the sixth framework program of the European Commission dedicated to the search for novel biomarker candidates for Alzheimer's disease and other neurodegenerative diseases. The ultimate goal of cNEUPRO is to identify one or more valid biomarker(s) in blood and CSF applicable to support the early and differential diagnosis of dementia disorders. The consortium covers all steps required for the discovery of novel biomarker candidates such as acquisition of high quality CSF and blood samples from relevant patient groups and controls, analysis of body fluids by various methods, and finally assay development and assay validation. Here we report the standardized procedures for diagnosis and preanalytical sample-handling within the project, as well as the status of the ongoing research activities and some first results.

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Sharma, Chanchal, Hanwoong Woo, and Sang Ryong Kim. "Addressing Blood–Brain Barrier Impairment in Alzheimer’s Disease." Biomedicines 10, no. 4 (March 22, 2022): 742. http://dx.doi.org/10.3390/biomedicines10040742.

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The blood–brain barrier (BBB) plays a vital role in maintaining the specialized microenvironment of the brain tissue. It facilitates communication while separating the peripheral circulation system from the brain parenchyma. However, normal aging and neurodegenerative diseases can alter and damage the physiological properties of the BBB. In this review, we first briefly present the essential pathways maintaining and regulating BBB integrity, and further review the mechanisms of BBB breakdown associated with normal aging and peripheral inflammation-causing neurodegeneration and cognitive impairments. We also discuss how BBB disruption can cause or contribute to Alzheimer’s disease (AD), the most common form of dementia and a devastating neurological disorder. Next, we document overlaps between AD and vascular dementia (VaD) and briefly sum up the techniques for identifying biomarkers linked to BBB deterioration. Finally, we conclude that BBB breakdown could be used as a biomarker to help diagnose cognitive impairment associated with normal aging and neurodegenerative diseases such as AD.

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Villain, Nicolas, and Bruno Dubois. "Alzheimer's Disease Including Focal Presentations." Seminars in Neurology 39, no. 02 (March 29, 2019): 213–26. http://dx.doi.org/10.1055/s-0039-1681041.

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AbstractAlzheimer's disease (AD) is the commonest neurodegenerative disease and the most frequent cause of dementia. It affects 30 million people worldwide. Current research criteria focus on biomarkers' status for amyloid and tau using positron emission tomography and cerebrospinal fluid analysis, independent of clinical status. Current epidemiological data, which mostly rely on biomarker-undetermined AD cases, have highlighted ApoE4 and age as the main risk factors. Rare autosomal dominant mutations also account for a small fraction of early-onset AD. The main clinical phenotype at presentation is the amnestic phenotype targeting episodic memory. This is followed by rarer phenotypes such as posterior cortical atrophy, logopenic variant of primary progressive aphasia, frontal variant AD, corticobasal syndrome, and other even rarer presentations mimicking language variants of frontotemporal dementia. Main differential diagnoses include hippocampal sclerosis with TDP-43, primary age-related tauopathy, argyrophilic grain disease, frontotemporal lobar degeneration, Lewy body disease, chronic traumatic encephalopathy as well as nondegenerative disorders such as cerebrovascular disease, chronic alcohol consumption, limbic encephalitis, medial temporal lobe epilepsy, and others. Co-occurrence of AD pathology with other neurodegenerative and vascular diseases is common and increases with age. This presents a challenge in current clinical practice due to a lack of reliable biomarkers for non-AD neurodegenerative diseases.

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Lake, Julie, Catherine S. Storm, Mary B. Makarious, and Sara Bandres-Ciga. "Genetic and Transcriptomic Biomarkers in Neurodegenerative Diseases: Current Situation and the Road Ahead." Cells 10, no. 5 (April 27, 2021): 1030. http://dx.doi.org/10.3390/cells10051030.

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Neurodegenerative diseases are etiologically and clinically heterogeneous conditions, often reflecting a spectrum of disease rather than well-defined disorders. The underlying molecular complexity of these diseases has made the discovery and validation of useful biomarkers challenging. The search of characteristic genetic and transcriptomic indicators for preclinical disease diagnosis, prognosis, or subtyping is an area of ongoing effort and interest. The next generation of biomarker studies holds promise by implementing meaningful longitudinal and multi-modal approaches in large scale biobank and healthcare system scale datasets. This work will only be possible in an open science framework. This review summarizes the current state of genetic and transcriptomic biomarkers in Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis, providing a comprehensive landscape of recent literature and future directions.

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Roy, Bidisha, Erica Lee, Teresa Li, and Maria Rampersaud. "Role of miRNAs in Neurodegeneration: From Disease Cause to Tools of Biomarker Discovery and Therapeutics." Genes 13, no. 3 (February 25, 2022): 425. http://dx.doi.org/10.3390/genes13030425.

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Neurodegenerative diseases originate from neuronal loss in the central nervous system (CNS). These debilitating diseases progress with age and have become common due to an increase in longevity. The National Institute of Environmental Health Science’s 2021 annual report suggests around 6.2 million Americans are living with Alzheimer’s disease, and there is a possibility that there will be 1.2 million Parkinson’s disease patients in the USA by 2030. There is no clear-cut universal mechanism for identifying neurodegenerative diseases, and therefore, they pose a challenge for neurobiology scientists. Genetic and environmental factors modulate these diseases leading to familial or sporadic forms. Prior studies have shown that miRNA levels are altered during the course of the disease, thereby suggesting that these noncoding RNAs may be the contributing factor in neurodegeneration. In this review, we highlight the role of miRNAs in the pathogenesis of neurodegenerative diseases. Through this review, we aim to achieve four main objectives: First, we highlight how dysregulation of miRNA biogenesis led to these diseases. Second, we highlight the computational or bioinformatics tools required to identify the putative molecular targets of miRNAs, leading to biological molecular pathways or mechanisms involved in these diseases. Third, we focus on the dysregulation of miRNAs and their target genes leading to several neurodegenerative diseases. In the final section, we highlight the use of miRNAs as potential diagnostic biomarkers in the early asymptomatic preclinical diagnosis of these age-dependent debilitating diseases. Additionally, we discuss the challenges and advances in the development of miRNA therapeutics for brain targeting. We list some of the innovative strategies employed to deliver miRNA into target cells and the relevance of these viral and non-viral carrier systems in RNA therapy for neurodegenerative diseases. In summary, this review highlights the relevance of studying brain-enriched miRNAs, the mechanisms underlying their regulation of target gene expression, their dysregulation leading to progressive neurodegeneration, and their potential for biomarker marker and therapeutic intervention. This review thereby highlights ways for the effective diagnosis and prevention of these neurodegenerative disorders in the near future.

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Kaur, Gagandeep, Suraj Singh S. Rathod, Mohammed M. Ghoneim, Sultan Alshehri, Javed Ahmad, Awanish Mishra, and Nabil A. Alhakamy. "DNA Methylation: A Promising Approach in Management of Alzheimer’s Disease and Other Neurodegenerative Disorders." Biology 11, no. 1 (January 7, 2022): 90. http://dx.doi.org/10.3390/biology11010090.

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DNA methylation, in the mammalian genome, is an epigenetic modification that involves the transfer of a methyl group on the C5 position of cytosine to derive 5-methylcytosine. The role of DNA methylation in the development of the nervous system and the progression of neurodegenerative diseases such as Alzheimer’s disease has been an interesting research area. Furthermore, mutations altering DNA methylation affect neurodevelopmental functions and may cause the progression of several neurodegenerative diseases. Epigenetic modifications in neurodegenerative diseases are widely studied in different populations to uncover the plausible mechanisms contributing to the development and progression of the disease and detect novel biomarkers for early prognosis and future pharmacotherapeutic targets. In this manuscript, we summarize the association of DNA methylation with the pathogenesis of the most common neurodegenerative diseases, such as, Alzheimer’s disease, Parkinson’s disease, Huntington diseases, and amyotrophic lateral sclerosis, and discuss the potential of DNA methylation as a potential biomarker and therapeutic tool for neurogenerative diseases.

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Dzieciatkowska, Monika, Guihong Qi, Jinsam You, Kerry G. Bemis, Heather Sahm, Howard M. Lederman, Thomas O. Crawford, Lawrence M. Gelbert, Cynthia Rothblum-Oviatt, and Mu Wang. "Proteomic Characterization of Cerebrospinal Fluid from Ataxia-Telangiectasia (A-T) Patients Using a LC/MS-Based Label-Free Protein Quantification Technology." International Journal of Proteomics 2011 (June 23, 2011): 1–13. http://dx.doi.org/10.1155/2011/578903.

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Cerebrospinal fluid (CSF) has been used for biomarker discovery of neurodegenerative diseases in humans since biological changes in the brain can be seen in this biofluid. Inactivation of A-T-mutated protein (ATM), a multifunctional protein kinase, is responsible for A-T, yet biochemical studies have not succeeded in conclusively identifying the molecular mechanism(s) underlying the neurodegeneration seen in A-T patients or the proteins that can be used as biomarkers for neurologic assessment of A-T or as potential therapeutic targets. In this study, we applied a high-throughput LC/MS-based label-free protein quantification technology to quantitatively characterize the proteins in CSF samples in order to identify differentially expressed proteins that can serve as potential biomarker candidates for A-T. Among 204 identified CSF proteins with high peptide-identification confidence, thirteen showed significant protein expression changes. Bioinformatic analysis revealed that these 13 proteins are either involved in neurodegenerative disorders or cancer. Future molecular and functional characterization of these proteins would provide more insights into the potential therapeutic targets for the treatment of A-T and the biomarkers that can be used to monitor or predict A-T disease progression. Clinical validation studies are required before any of these proteins can be developed into clinically useful biomarkers.

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Puranik, Nidhi, Dhananjay Yadav, Shiv Kumar Yadav, Vishal K. Chavda, and Jun-O. Jin. "Proteomics and Neurodegenerative Disorders: Advancements in the Diagnostic Analysis." Current Protein & Peptide Science 21, no. 12 (December 31, 2020): 1174–83. http://dx.doi.org/10.2174/1389203721666200511094222.

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: Changes in protein structure and function, alteration in protein-protein interaction, and significant difference in protein concentration inside the body could play an important role in indicating the pathological evidence of abnormalities before the development of clinical symptoms and act as a critical detection and diagnostic tool commonly known as biomarkers. Biomarkers play important roles in the diagnosis of various chronic diseases, including cancer. Neurodegenerative disorders, including Parkinson's, Alzheimer's, Huntington's, prion, and multiple sclerosis, are well characterized by neuronal deterioration, resulting in precise modifications of neuronal proteins. Nowadays, the diagnosis of neurological disorders is based on proteins or biomarkers. These biomarkers may be found in the cerebrospinal fluid, blood, serum, plasma, saliva, or urine sample. Early diagnosis is urgently needed to prevent further damage. For early diagnosis, identifying the changes in novel protein levels and their functions under the disease conditions is necessary. These can be used as specific proteomic biomarkers for diseases, and they can be possibly identified using neuroproteomics. Neuroproteomics is an emerging tool to corroborate disease-associated protein profiles. It also gives an idea about how these proteins interact with other proteins and undergo post-translational modifications. Neuroproteomics is based on bioinformatics, which provides functional characteristics and advances in technology such as mass spectroscopy, and can help in the discovery of various disease-specific biomarkers. This review gives a complete idea about the types of biomarkers, sources of biomarkers, and techniques involved in the discovery of biomarkers for early diagnosis of neurodegenerative diseases.

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Zhao, Xiangli, Sadaf Hasan, Benjamin Liou, Yi Lin, Ying Sun, and Chuanju Liu. "Analysis of the Biomarkers for Neurodegenerative Diseases in Aged Progranulin Deficient Mice." International Journal of Molecular Sciences 23, no. 2 (January 6, 2022): 629. http://dx.doi.org/10.3390/ijms23020629.

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Neurodegenerative diseases are debilitating impairments that affect millions of people worldwide and are characterized by progressive degeneration of structure and function of the central or peripheral nervous system. Effective biomarkers for neurodegenerative diseases can be used to improve the diagnostic workup in the clinic as well as facilitate the development of effective disease-modifying therapies. Progranulin (PGRN) has been reported to be involved in various neurodegenerative disorders. Hence, in the current study we systematically compared the inflammation and accumulation of typical neurodegenerative disease markers in the brain tissue between PGRN knockout (PGRN KO) and wildtype (WT) mice. We found that PGRN deficiency led to significant neuron loss as well as activation of microglia and astrocytes in aged mice. Several characteristic neurodegenerative markers, including α-synuclein, TAR DNA-binding protein 43 (TDP-43), Tau, and β-amyloid, were all accumulated in the brain of PGRN-deficient mice as compared to WT mice. Moreover, higher aggregation of lipofuscin was observed in the brain tissue of PGRN-deficient mice compared with WT mice. In addition, the autophagy was also defective in the brain of PGRN-deficient mice, indicated by the abnormal expression level of autophagy marker LC3-II. Collectively, comprehensive assays support the idea that PGRN plays an important role during the development of neurodegenerative disease, indicating that PGRN might be a useful biomarker for neurodegenerative diseases in clinical settings.

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Doroszkiewicz, Julia, Magdalena Groblewska, and Barbara Mroczko. "Molecular Biomarkers and Their Implications for the Early Diagnosis of Selected Neurodegenerative Diseases." International Journal of Molecular Sciences 23, no. 9 (April 21, 2022): 4610. http://dx.doi.org/10.3390/ijms23094610.

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The degeneration and dysfunction of neurons are key features of neurodegenerative diseases (NDs). Currently, one of the main challenges facing researchers and clinicians is the ability to obtain reliable diagnostic tools that will allow for the diagnosis of NDs as early as possible and the detection of neuronal dysfunction, preferably in the presymptomatic stage. Additionally, better tools for assessing disease progression in this group of disorders are also being sought. The ideal biomarker must have high sensitivity and specificity, be easy to measure, give reproducible results, and reflect the disease progression. Molecular biomarkers include miRNAs and extracellular microvesicles known as exosomes. They may be measured in two extracellular fluids of the highest importance in NDs, i.e., cerebrospinal fluid (CSF) and blood. The aim of the current review is to summarize the pathophysiology of the four most frequent NDs—i.e., Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)—as well as current progress in the research into miRNAs as biomarkers in these major neurodegenerative diseases. In addition, we discuss the possibility of using miRNA-based therapies in the treatment of neurodegenerative diseases, and present the limitations of this type of therapy.

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Swann, Owen James, Michael Turner, Amanda Heslegrave, and Henrik Zetterberg. "Fluid biomarkers and risk of neurodegenerative disease in retired athletes with multiple concussions: results from the International Concussion and Head Injury Research Foundation Brain health in Retired athletes Study of Ageing and Impact-Related Neurodegenerative Disease (ICHIRF-BRAIN study)." BMJ Open Sport & Exercise Medicine 8, no. 3 (September 2022): e001327. http://dx.doi.org/10.1136/bmjsem-2022-001327.

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ObjectivesTo investigate the association and utility of blood plasma markers of neurodegeneration in a population of retired athletes self-reporting multiple concussions throughout a sporting career. It is hypothesised that this type of athletic history would cause an increased prevalence of neurodegenerative disease, as detected by biomarkers for neurodegenerative disease processes.MethodsOne hundred and fifty-nine participants were recruited (90 males, 69 females, mean age 61.3±9.13 years), including 121 participants who had retired from playing professional or semiprofessional sports and self-reported ≥1 concussion during their careers (range 1–74; mean concussions=10.7). The control group included 38 age-matched and sex-matched controls, with no history of concussion. We measured neurofilament light (NfL) and tau (neurodegeneration markers), glial fibrillar acidic protein (GFAP) (astrocytic activation marker) and 40 and 42 amino acid-long amyloid beta (Aβ40 and Aβ42) (Alzheimer-associated amyloid pathology markers) concentrations using ultrasensitive single molecule array technology.ResultsWe found retired athletes reporting one or more concussions throughout an athletic career showed no significant changes in NfL, tau, GFAP and Aβ40 and Aβ42 concentrations in comparison to a control group. No correlations were found between biomarkers and number of concussions (mean=10.7). A moderate correlation was found between NfL concentration and age.ConclusionNo difference in blood concentrations of neurodegeneration markers NfL, tau, GFAP and Aβ40 and Aβ42 was found in retired athletes with a history of concussion compared with controls. An increased prevalence of neurodegenerative diseases is not detected by biomarkers in a population self-reporting multiple concussions.Trial registration numberISRCTN 11312093

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Hosaka, Takashi, Takenari Yamashita, Akira Tamaoka, and Shin Kwak. "Extracellular RNAs as Biomarkers of Sporadic Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases." International Journal of Molecular Sciences 20, no. 13 (June 27, 2019): 3148. http://dx.doi.org/10.3390/ijms20133148.

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Recent progress in the research for underlying mechanisms in neurodegenerative diseases, including Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) has led to the development of potentially effective treatment, and hence increased the need for useful biomarkers that may enable early diagnosis and therapeutic monitoring. The deposition of abnormal proteins is a pathological hallmark of neurodegenerative diseases, including β-amyloid in AD, α-synuclein in PD, and the transactive response DNA/RNA binding protein of 43kDa (TDP-43) in ALS. Furthermore, progression of the disease process accompanies the spreading of abnormal proteins. Extracellular proteins and RNAs, including mRNA, micro RNA, and circular RNA, which are present as a composite of exosomes or other forms, play a role in cell–cell communication, and the role of extracellular molecules in the cell-to-cell spreading of pathological processes in neurodegenerative diseases is now in the spotlight. Therefore, extracellular proteins and RNAs are considered potential biomarkers of neurodegenerative diseases, in particular ALS, in which RNA dysregulation has been shown to be involved in the pathogenesis. Here, we review extracellular proteins and RNAs that have been scrutinized as potential biomarkers of neurodegenerative diseases, and discuss the possibility of extracellular RNAs as diagnostic and therapeutic monitoring biomarkers of sporadic ALS.

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Satue, Maria, Javier Obis, Maria J. Rodrigo, Sofia Otin, Maria I. Fuertes, Elisa Vilades, Hector Gracia, et al. "Optical Coherence Tomography as a Biomarker for Diagnosis, Progression, and Prognosis of Neurodegenerative Diseases." Journal of Ophthalmology 2016 (2016): 1–9. http://dx.doi.org/10.1155/2016/8503859.

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Neurodegenerative diseases present a current challenge for accurate diagnosis and for providing precise prognostic information. Developing imaging biomarkers for multiple sclerosis (MS), Parkinson disease (PD), and Alzheimer’s disease (AD) will improve the clinical management of these patients and may be useful for monitoring treatment effectiveness. Recent research using optical coherence tomography (OCT) has demonstrated that parameters provided by this technology may be used as potential biomarkers for MS, PD, and AD. Retinal thinning has been observed in these patients and new segmentation software for the analysis of the different retinal layers may provide accurate information on disease progression and prognosis. In this review we analyze the application of retinal evaluation using OCT technology to provide better understanding of the possible role of the retinal layers thickness as biomarker for the detection of these neurodegenerative pathologies. Current OCT analysis of the retinal nerve fiber layer and, specially, the ganglion cell layer thickness may be considered as a good biomarker for disease diagnosis, severity, and progression.

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Pawlik, Patrycja, and Katarzyna Błochowiak. "The Role of Salivary Biomarkers in the Early Diagnosis of Alzheimer’s Disease and Parkinson’s Disease." Diagnostics 11, no. 2 (February 22, 2021): 371. http://dx.doi.org/10.3390/diagnostics11020371.

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Many neurodegenerative diseases present with progressive neuronal degeneration, which can lead to cognitive and motor impairment. Early screening and diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are necessary to begin treatment before the onset of clinical symptoms and slow down the progression of the disease. Biomarkers have shown great potential as a diagnostic tool in the early diagnosis of many diseases, including AD and PD. However, screening for these biomarkers usually includes invasive, complex and expensive methods such as cerebrospinal fluid (CSF) sampling through a lumbar puncture. Researchers are continuously seeking to find a simpler and more reliable diagnostic tool that would be less invasive than CSF sampling. Saliva has been studied as a potential biological fluid that could be used in the diagnosis and early screening of neurodegenerative diseases. This review aims to provide an insight into the current literature concerning salivary biomarkers used in the diagnosis of AD and PD. The most commonly studied salivary biomarkers in AD are β-amyloid1-42/1-40 and TAU protein, as well as α-synuclein and protein deglycase (DJ-1) in PD. Studies continue to be conducted on this subject and researchers are attempting to find correlations between specific biomarkers and early clinical symptoms, which could be key in creating new treatments for patients before the onset of symptoms.

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Zarrouk, Amira, Meryam Debbabi, Maryem Bezine, El Mostafa Karym, Asmaa Badreddine, Olivier Rouaud, Thibault Moreau, et al. "Lipid Biomarkers in Alzheimer's Disease." Current Alzheimer Research 15, no. 4 (February 22, 2018): 303–12. http://dx.doi.org/10.2174/1567205014666170505101426.

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Background: There are now significant evidences that lipid metabolism is affected in numerous neurodegenerative diseases including Alzheimer’s disease. These dysfunctions lead to abnormal levels of certain lipids in the brain, cerebrospinal fluid and plasma. It is consequently of interest to establish lipid profiles in neurodegenerative diseases. This approach, which can contribute to identify lipid biomarkers of Alzheimers' disease, can also permit to identify new therapeutic targets. It was therefore of interest to focus on central and peripheral biomarkers in Alzheimer's disease. Methods: A review of the literature on 148 papers was conducted. Based on this literature, the involvement of lipids (cholesterol and oxysterols, fatty acids, phospholipids) in Alzheimer's disease has been proposed. Results: Of the 148 references cited for lipid biomarkers for Alzheimer's disease, 65 refer to cholesterol and oxysterols, 35 to fatty acids and 40 to phospholipids. Among these lipids, some of them such as 24S-hydroxyckolesterol, open up new therapeutic perspectives in gene therapy, in particular. The results on the very long-chain fatty acids suggest the potential of peroxisomal dysfunctions in Alzheimer's disease. As for the phospholipids, they could constitute interesting biomarkers for detecting the disease at the prodromal stage. Conclusion: There are now several lines of evidence that lipids play fundamental roles in the pathogenesis of AD and that some of them have a prognostic and diagnosis value. This may pave the way for the identification of new therapeutic targets, new effective drugs and / or new treatments.

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van Oostveen, Wieke M., and Elizabeth C. M. de Lange. "Imaging Techniques in Alzheimer’s Disease: A Review of Applications in Early Diagnosis and Longitudinal Monitoring." International Journal of Molecular Sciences 22, no. 4 (February 20, 2021): 2110. http://dx.doi.org/10.3390/ijms22042110.

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Background. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting many individuals worldwide with no effective treatment to date. AD is characterized by the formation of senile plaques and neurofibrillary tangles, followed by neurodegeneration, which leads to cognitive decline and eventually death. Introduction. In AD, pathological changes occur many years before disease onset. Since disease-modifying therapies may be the most beneficial in the early stages of AD, biomarkers for the early diagnosis and longitudinal monitoring of disease progression are essential. Multiple imaging techniques with associated biomarkers are used to identify and monitor AD. Aim. In this review, we discuss the contemporary early diagnosis and longitudinal monitoring of AD with imaging techniques regarding their diagnostic utility, benefits and limitations. Additionally, novel techniques, applications and biomarkers for AD research are assessed. Findings. Reduced hippocampal volume is a biomarker for neurodegeneration, but atrophy is not an AD-specific measure. Hypometabolism in temporoparietal regions is seen as a biomarker for AD. However, glucose uptake reflects astrocyte function rather than neuronal function. Amyloid-β (Aβ) is the earliest hallmark of AD and can be measured with positron emission tomography (PET), but Aβ accumulation stagnates as disease progresses. Therefore, Aβ may not be a suitable biomarker for monitoring disease progression. The measurement of tau accumulation with PET radiotracers exhibited promising results in both early diagnosis and longitudinal monitoring, but large-scale validation of these radiotracers is required. The implementation of new processing techniques, applications of other imaging techniques and novel biomarkers can contribute to understanding AD and finding a cure. Conclusions. Several biomarkers are proposed for the early diagnosis and longitudinal monitoring of AD with imaging techniques, but all these biomarkers have their limitations regarding specificity, reliability and sensitivity. Future perspectives. Future research should focus on expanding the employment of imaging techniques and identifying novel biomarkers that reflect AD pathology in the earliest stages.

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Castanedo-Cazares, Juan Pablo, and Idelfonso Rodriguez-Leyva. "Skin biomarkers for neurodegenerative disease: a future perspective." Neurodegenerative Disease Management 5, no. 6 (December 2015): 465–67. http://dx.doi.org/10.2217/nmt.15.51.

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Thompson, Alexander G., Elizabeth Gray, Sabrina M. Heman-Ackah, Imre Mäger, Kevin Talbot, Samir El Andaloussi, Matthew J. Wood, and Martin R. Turner. "Extracellular vesicles in neurodegenerative disease — pathogenesis to biomarkers." Nature Reviews Neurology 12, no. 6 (May 13, 2016): 346–57. http://dx.doi.org/10.1038/nrneurol.2016.68.

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Calvo, Ana C., Raquel Manzano, Deise M. F. Mendonça, María J. Muñoz, Pilar Zaragoza, and Rosario Osta. "Amyotrophic Lateral Sclerosis: A Focus on Disease Progression." BioMed Research International 2014 (2014): 1–12. http://dx.doi.org/10.1155/2014/925101.

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Since amyotrophic lateral sclerosis (ALS) was discovered and described in 1869 as a neurodegenerative disease in which motor neuron death is induced, a wide range of biomarkers have been selected to identify therapeutic targets. ALS shares altered molecular pathways with other neurodegenerative diseases, such as Alzheimer’s, Huntington’s, and Parkinson’s diseases. However, the molecular targets that directly influence its aggressive nature remain unknown. What is the first link in the neurodegenerative chain of ALS that makes this disease so peculiar? In this review, we will discuss the progression of the disease from the viewpoint of the potential biomarkers described to date in human and animal model samples. Finally, we will consider potential therapeutic strategies for ALS treatment and future, innovative perspectives.

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Seol, Wongi, Hyejung Kim, and Ilhong Son. "Urinary Biomarkers for Neurodegenerative Diseases." Experimental Neurobiology 29, no. 5 (October 31, 2020): 325–33. http://dx.doi.org/10.5607/en20042.

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STANESCU, Ioana, Adriana BULBOACĂ, Gabriela, DOGARU, and Cristina NICULA. "Tear biomarkers in neurodegenerative diseases." Balneo Research Journal 11, no. 3 (May 10, 2020): 191–95. http://dx.doi.org/10.12680/balneo.2020.339.

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Ciaccio, Marcello. "Biochemical Biomarkers and Neurodegenerative Diseases." Brain Sciences 11, no. 7 (July 16, 2021): 940. http://dx.doi.org/10.3390/brainsci11070940.

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Neurodegenerative diseases (ND) are a heterogeneous group of disorders characterized by progressive dysfunction and loss of neurons in different areas of the central nervous system or peripheral nervous system [...]

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Valenti, Denise A. "Alzheimer's Disease and Glaucoma: Imaging the Biomarkers of Neurodegenerative Disease." International Journal of Alzheimer's Disease 2010 (2010): 1–9. http://dx.doi.org/10.4061/2010/793931.

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Imaging through the visual system in Alzheimer's disease, with the technology currently in widespread use for the diagnosis and management of eye disease such as glaucoma and macular degeneration, is proving to be promising. In vivo cross-section imaging during an annual comprehensive eye exam has been available for a decade for glaucoma and macular degeneration, and this same imaging, using Optical Coherence Tomography, has been demonstrated to show deficits specific to AD and mild cognitive impairment. These deficits are in the form of nerve fiber layer tissue drop out in the retina and optic nerve. The retrograde loss of nerve fiber layer tissue in the retina and optic nerve may be an early biomarker of AD, and these deficits in the nerve fiber layer of the retina and optic nerve may be the earliest sign of AD, even prior to damage to the hippocampal region that impacts memory.

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Manna, Ida, Selene De Benedittis, Andrea Quattrone, Domenico Maisano, Enrico Iaccino, and Aldo Quattrone. "Exosomal miRNAs as Potential Diagnostic Biomarkers in Alzheimer’s Disease." Pharmaceuticals 13, no. 9 (September 12, 2020): 243. http://dx.doi.org/10.3390/ph13090243.

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Alzheimer’s disease (AD), a neurodegenerative disease, is linked to a variety of internal and external factors present from the early stages of the disease. There are several risk factors related to the pathogenesis of AD, among these exosomes and microRNAs (miRNAs) are of particular importance. Exosomes are nanocarriers released from many different cell types, including neuronal cells. Through the transfer of bioactive molecules, they play an important role both in the maintenance of physiological and in pathological conditions. Exosomes could be carriers of potential biomarkers useful for the assessment of disease progression and for therapeutic applications. miRNAs are small noncoding endogenous RNA sequences active in the regulation of protein expression, and alteration of miRNA expression can result in a dysregulation of key genes and pathways that contribute to disease development. Indeed, the involvement of exosomal miRNAs has been highlighted in various neurodegenerative diseases, and this opens the possibility that dysregulated exosomal miRNA profiles may influence AD disease. The advances in exosome-related biomarker detection in AD are summarized. Finally, in this review, we highlight the use of exosomal miRNAs as essential biomarkers in preclinical and clinical studies in Alzheimer’s disease, also taking a look at their potential clinical value.

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Zetterberg, Henrik. "Applying fluid biomarkers to Alzheimer's disease." American Journal of Physiology-Cell Physiology 313, no. 1 (July 1, 2017): C3—C10. http://dx.doi.org/10.1152/ajpcell.00007.2017.

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Alzheimer’s disease (AD) is a common neurodegenerative disease that starts with a clinically silent phase of a decade or more during which brain pathologies accumulate predominantly in the medial temporal lobe but also elsewhere in the brain. Network dysfunction and clinical symptoms typically appear when senile plaque (amyloid-β) and neurofibrillary tangle (tau) pathologies meet in the brain parenchyma, producing synapse and neuronal loss. For plaque and tangle pathologies, reliable fluid biomarkers have been developed. These require sampling of cerebrospinal fluid. Reliable blood tests for plaque and tangle pathologies are currently lacking, but blood tests for general neurodegeneration have recently been developed. In AD, plaques and tangles often coexist with other pathologies, including Lewy bodies, and to what extent these contribute to symptoms is currently unknown. There are also important differential diagnoses that may be possible to distinguish from AD with the aid of biomarkers. The scope of this review is fluid biomarkers for AD and related pathologies. The purpose is to provide the reader with an updated account of currently available fluid biomarkers for AD and clinically relevant differential diagnoses.

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Del Prete, Eleonora, Maria Francesca Beatino, Nicole Campese, Linda Giampietri, Gabriele Siciliano, Roberto Ceravolo, and Filippo Baldacci. "Fluid Candidate Biomarkers for Alzheimer’s Disease: A Precision Medicine Approach." Journal of Personalized Medicine 10, no. 4 (November 11, 2020): 221. http://dx.doi.org/10.3390/jpm10040221.

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A plethora of dynamic pathophysiological mechanisms underpins highly heterogeneous phenotypes in the field of dementia, particularly in Alzheimer’s disease (AD). In such a faceted scenario, a biomarker-guided approach, through the implementation of specific fluid biomarkers individually reflecting distinct molecular pathways in the brain, may help establish a proper clinical diagnosis, even in its preclinical stages. Recently, ultrasensitive assays may detect different neurodegenerative mechanisms in blood earlier. ß-amyloid (Aß) peptides, phosphorylated-tau (p-tau), and neurofilament light chain (NFL) measured in blood are gaining momentum as candidate biomarkers for AD. P-tau is currently the more convincing plasma biomarker for the diagnostic workup of AD. The clinical role of plasma Aβ peptides should be better elucidated with further studies that also compare the accuracy of the different ultrasensitive techniques. Blood NFL is promising as a proxy of neurodegeneration process tout court. Protein misfolding amplification assays can accurately detect α-synuclein in cerebrospinal fluid (CSF), thus representing advancement in the pathologic stratification of AD. In CSF, neurogranin and YKL-40 are further candidate biomarkers tracking synaptic disruption and neuroinflammation, which are additional key pathophysiological pathways related to AD genesis. Advanced statistical analysis using clinical scores and biomarker data to bring together individuals with AD from large heterogeneous cohorts into consistent clusters may promote the discovery of pathophysiological causes and detection of tailored treatments.

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Crotty, Grace. "Biomarkers in Parkinson’s disease." Boolean: Snapshots of Doctoral Research at University College Cork, no. 2014 (January 1, 2014): 7–12. http://dx.doi.org/10.33178/boolean.2014.2.

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Do you know anyone who has been diagnosed with Parkinson’s disease? What is Parkinson’s disease? In the Department of Medicine in UCC I am carrying out research on this condition, and I’m working with people who have Parkinson’s disease (PD). I hope to increase our understanding of the disease mechanisms underlying PD along with identifying potential biomarkers for PD. What are biomarkers? Why do we need a biomarker? Keep on reading to discover more! It is the second most common age-related neurodegenerative condition after Alzheimer’s disease. It affects 1% of people over 65 years and 4% over 80 years. 30 million people are currently affected worldwide. It was first described by Dr. James Parkinson in 1817 in his book “An Essay on the shaking palsy”. Parkinson’s disease occurs when there is not enough of a chemical called dopamine being produced by your brain. People with PD classically present to their ...

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Briganti, Stefania, Mauro Truglio, Antonella Angiolillo, Salvatore Lombardo, Deborah Leccese, Emanuela Camera, Mauro Picardo, and Alfonso Di Costanzo. "Application of Sebum Lipidomics to Biomarkers Discovery in Neurodegenerative Diseases." Metabolites 11, no. 12 (November 29, 2021): 819. http://dx.doi.org/10.3390/metabo11120819.

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Lipidomics is strategic in the discovery of biomarkers of neurodegenerative diseases (NDDs). The skin surface lipidome bears the potential to provide biomarker candidates in the detection of pathological processes occurring in distal organs. We investigated the sebum composition to search diagnostic and, possibly, prognostic, biomarkers of Alzheimer’s disease (AD) and Parkinson’s disease (PD). The observational study included 64 subjects: 20 characterized as “probable AD with documented decline”, 20 as “clinically established PD”, and 24 healthy subjects (HS) of comparable age. The analysis of sebum by GCMS and TLC retrieved the amounts (µg) of 41 free fatty acids (FFAs), 7 fatty alcohols (FOHs), vitamin E, cholesterol, squalene, and total triglycerides (TGs) and wax esters (WEs). Distributions of sebum lipids in NDDs and healthy conditions were investigated with multivariate ANOVA-simultaneous component analysis (ASCA). The deranged sebum composition associated with the PD group showed incretion of most composing lipids compared to HS, whereas only two lipid species (vitamin E and FOH14:0) were discriminant of AD samples and presented lower levels than HS sebum. Thus, sebum lipid biosynthetic pathways are differently affected in PD and AD. The characteristic sebum bio-signatures detected support the value of sebum lipidomics in the biomarkers search in NDDs.

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Sheikh, Saba, Safia, Ejazul Haque, and Snober S. Mir. "Neurodegenerative Diseases: Multifactorial Conformational Diseases and Their Therapeutic Interventions." Journal of Neurodegenerative Diseases 2013 (December 30, 2013): 1–8. http://dx.doi.org/10.1155/2013/563481.

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Neurodegenerative diseases are multifactorial debilitating disorders of the nervous system that affect approximately 30 millionindividuals worldwide. Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis diseases are the consequence of misfolding and dysfunctional trafficking of proteins. Beside that, mitochondrial dysfunction, oxidative stress, and/or environmental factors strongly associated with age have also been implicated in causing neurodegeneration. After years of intensive research, considerable evidence has accumulated that demonstrates an important role of these factors in the etiology of common neurodegenerative diseases. Despite the extensive efforts that have attempted to define the molecular mechanisms underlying neurodegeneration, many aspects of these pathologies remain elusive. However, in order to explore the therapeutic interventions directed towards treatment of neurodegenerative diseases, neuroscientists are now fully exploiting the data obtained from studies of these basic mechanisms that have gone awry. The novelty of these mechanisms represents a challenge to the identification of viable drug targets and biomarkers for early diagnosis of the diseases. In this paper, we are reviewing various aspects associated with the disease and the recent trends that may have an application for the treatment of the neurodegenerative disorders.

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Dubuisson, Nicolas, Fabiola Puentes, Gavin Giovannoni, and Sharmilee Gnanapavan. "Science is 1% inspiration and 99% biomarkers." Multiple Sclerosis Journal 23, no. 11 (May 24, 2017): 1442–52. http://dx.doi.org/10.1177/1352458517709362.

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Neurodegeneration plays a key role in multiple sclerosis (MS) contributing to long-term disability in patients. The prognosis is, however, unpredictable coloured by complex disease mechanisms which can only be clearly appreciated using biomarkers specific to pathobiology of the underlying process. Here, we describe six promising neurodegenerative biomarkers in MS (neurofilament proteins, neurofilament antibodies, tau, N-acetylaspartate, chitinase and chitinase-like proteins and osteopontin), critically evaluating the evidence using a modified Bradford Hill criteria.

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Journal articles on the topic 'Biomarkers of neurodegenerative disease'

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