Relevant bibliographies by topics / Amyloid beta-protein Pathophysiology

Academic literature on the topic 'Amyloid beta-protein Pathophysiology'

Author: Grafiati
Published: 10 December 2022
Last updated: 28 January 2023

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Contents

Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Amyloid beta-protein Pathophysiology.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Journal articles on the topic "Amyloid beta-protein Pathophysiology"

1

Ma, Chen, Fenfang Hong, and Shulong Yang. "Amyloidosis in Alzheimer’s Disease: Pathogeny, Etiology, and Related Therapeutic Directions." Molecules 27, no. 4 (February 11, 2022): 1210. http://dx.doi.org/10.3390/molecules27041210.

Full text
Abstract:
The amyloid hypothesis of Alzheimer’s disease has long been the predominant theory, suggesting that Alzheimer’s disease is caused by the accumulation of amyloid beta protein (Aβ) in the brain, leading to neuronal toxicity in the central nervous system (CNS). Because of breakthroughs in molecular medicine, the amyloid pathway is thought to be central to the pathophysiology of Alzheimer’s disease (AD). Currently, it is believed that altered biochemistry of the Aβ cycle remains a central biological feature of AD and is a promising target for treatment. This review provides an overview of the process of amyloid formation, explaining the transition from amyloid precursor protein to amyloid beta protein. Moreover, we also reveal the relationship between autophagy, cerebral blood flow, ACHE, expression of LRP1, and amyloidosis. In addition, we discuss the detailed pathogenesis of amyloidosis, including oxidative damage, tau protein, NFTs, and neuronal damage. Finally, we list some ways to treat AD in terms of decreasing the accumulation of Aβ in the brain.
APA, Harvard, Vancouver, ISO, and other styles
2

Alasmari, Fawaz, Musaad A. Alshammari, Abdullah F. Alasmari, Wael A. Alanazi, and Khalid Alhazzani. "Neuroinflammatory Cytokines Induce Amyloid Beta Neurotoxicity through Modulating Amyloid Precursor Protein Levels/Metabolism." BioMed Research International 2018 (October 25, 2018): 1–8. http://dx.doi.org/10.1155/2018/3087475.

Full text
Abstract:
Neuroinflammation has been observed in association with neurodegenerative diseases including Alzheimer’s disease (AD). In particular, a positive correlation has been documented between neuroinflammatory cytokine release and the progression of the AD, which suggests these cytokines are involved in AD pathophysiology. A histological hallmark of the AD is the presence of beta-amyloid (Aβ) plaques and tau neurofibrillary tangles. Beta-amyloid is generated by the sequential cleavage of beta (β) and gamma (γ) sites in the amyloid precursor protein (APP) by β- and γ-secretase enzymes and its accumulation can result from either a decreased Aβ clearance or increased metabolism of APP. Previous studies reported that neuroinflammatory cytokines reduce the efflux transport of Aβ, leading to elevated Aβ concentrations in the brain. However, less is known about the effects of neuroinflammatory mediators on APP expression and metabolism. In this article, we review the modulatory role of neuroinflammatory cytokines on APP expression and metabolism, including their effects on β- and γ-secretase enzymes.
APA, Harvard, Vancouver, ISO, and other styles
3

Gatti, Laura, Francesca Tinelli, Emma Scelzo, Francesco Arioli, Giuseppe Di Fede, Laura Obici, Leonardo Pantoni, et al. "Understanding the Pathophysiology of Cerebral Amyloid Angiopathy." International Journal of Molecular Sciences 21, no. 10 (May 13, 2020): 3435. http://dx.doi.org/10.3390/ijms21103435.

Full text
Abstract:
Cerebral amyloid angiopathy (CAA), one of the main types of cerebral small vessel disease, is a major cause of spontaneous intracerebral haemorrhage and an important contributor to cognitive decline in elderly patients. Despite the number of experimental in vitro studies and animal models, the pathophysiology of CAA is still largely unknown. Although several pathogenic mechanisms including an unbalance between production and clearance of amyloid beta (Aβ) protein as well as ‘the prion hypothesis’ have been invoked as possible disease triggers, they do not explain completely the disease pathogenesis. This incomplete disease knowledge limits the implementation of treatments able to prevent or halt the clinical progression. The continuous increase of CAA patients makes imperative the development of suitable experimental in vitro or animal models to identify disease biomarkers and new pharmacological treatments that could be administered in the early disease stages to prevent irreversible changes and disease progression.
APA, Harvard, Vancouver, ISO, and other styles
4

Carbone, Manuel Glauco, Giovanni Pagni, Claudia Tagliarini, Donatella Marazziti, and Nunzio Pomara. "Platelet APP Processing: Is It a Tool to Explore the Pathophysiology of Alzheimer’s Disease? A Systematic Review." Life 11, no. 8 (July 26, 2021): 750. http://dx.doi.org/10.3390/life11080750.

Full text
Abstract:
The processing of the amyloid precursor protein (APP) is a critical event in the formation of amyloid plaques. Platelets contain most of the enzymatic machinery required for APP processing and correlates of intracerebral abnormalities have been demonstrated in platelets of patients with AD. The goal of the present paper was to analyze studies exploring platelet APP metabolism in Alzheimer’s disease patients trying to assess potential reliable peripheral biomarkers, to offer new therapeutic solutions and to understand the pathophysiology of the AD. According to the PRISMA guidelines, we performed a systematic review through the PubMed database up to June 2020 with the search terms: “((((((APP) OR Amyloid Precursor Protein) OR AbetaPP) OR Beta Amyloid) OR Amyloid Beta) OR APP-processing) AND platelet”. Thirty-two studies were included in this systematic review. The papers included are analytic observational studies, namely twenty-nine cross sectional studies and three longitudinal studies, specifically prospective cohort study. The studies converge in an almost unitary way in affirming that subjects with AD show changes in APP processing compared to healthy age-matched controls. However, the problem of the specificity and sensitivity of these biomarkers is still at issue and would deserve to be deepened in future studies.
APA, Harvard, Vancouver, ISO, and other styles
5

LAGUNES, TERESA, MARISOL HERRERA-RIVERO, MARÍA ELENA HERNÁNDEZ-AGUILAR, and GONZALO E. ARANDA-ABREU. "Abeta(1-42) induces abnormal alternative splicing of tau exons 2/3 in NGF-induced PC12 cells." Anais da Academia Brasileira de Ciências 86, no. 4 (December 2014): 1927–34. http://dx.doi.org/10.1590/0001-3765201420130333.

Full text
Abstract:
Protein tau plays a pivotal role in the pathophysiology of Alzheimer's disease, where its hyperphos-phorylation promotes aggregation and microtubule destabilization. Tau undergoes alternative splicing which generates six isoforms in the human brain, due to inclusion/exclusion of exons 2, 3 and 10. Dysregulation of the splicing process of tau exon 10 is sufficient to cause tauopathy and has shown to be influenced by beta-amyloid peptides, but splicing of other exons is less studied. We studied the effects of beta-amyloid(42) in the alternative splicing of tau exons 2/3 and 6, using untreated and Nerve Growth Factor-induced PC12 cells. Beta-amyloid exposure caused formed cell processes to retract in differentiated cells and altered the expression of exons 2/3 in both undifferentiated and differentiated cells. Expression of exon 6 was repressed in undifferentiated cells only. Our results suggest that beta-amyloid interferes with the splicing process of exons 2/3, favoring their exclusion and thus the expression of immature tau isoforms that are less efficient in stabilizing microtubules and may also be more prone to hyperphosphorylation. The molecular mechanism for this amyloid-tau interaction remains to be determined, but may have potential implications for the understanding of the underlying neuropathological processes in Alzheimer's disease.
APA, Harvard, Vancouver, ISO, and other styles
6

Koike, Haruki, Yohei Iguchi, Kentaro Sahashi, and Masahisa Katsuno. "Significance of Oligomeric and Fibrillar Species in Amyloidosis: Insights into Pathophysiology and Treatment." Molecules 26, no. 16 (August 22, 2021): 5091. http://dx.doi.org/10.3390/molecules26165091.

Full text
Abstract:
Amyloidosis is a term referring to a group of various protein-misfolding diseases wherein normally soluble proteins form aggregates as insoluble amyloid fibrils. How, or whether, amyloid fibrils contribute to tissue damage in amyloidosis has been the topic of debate. In vitro studies have demonstrated the appearance of small globular oligomeric species during the incubation of amyloid beta peptide (Aβ). Nerve biopsy specimens from patients with systemic amyloidosis have suggested that globular structures similar to Aβ oligomers were generated from amorphous electron-dense materials and later developed into mature amyloid fibrils. Schwann cells adjacent to amyloid fibrils become atrophic and degenerative, suggesting that the direct tissue damage induced by amyloid fibrils plays an important role in systemic amyloidosis. In contrast, there is increasing evidence that oligomers, rather than amyloid fibrils, are responsible for cell death in neurodegenerative diseases, particularly Alzheimer’s disease. Disease-modifying therapies based on the pathophysiology of amyloidosis have now become available. Aducanumab, a human monoclonal antibody against the aggregated form of Aβ, was recently approved for Alzheimer’s disease, and other monoclonal antibodies, including gantenerumab, solanezumab, and lecanemab, could also be up for approval. As many other agents for amyloidosis will be developed in the future, studies to develop sensitive clinical scales for identifying improvement and markers that can act as surrogates for clinical scales should be conducted.
APA, Harvard, Vancouver, ISO, and other styles
7

Hultman, Karin, Sidney Strickland, and Erin H. Norris. "The APOE ε4/ε4 Genotype Potentiates Vascular Fibrin(Ogen) Deposition in Amyloid-Laden Vessels in the Brains of Alzheimer's Disease Patients." Journal of Cerebral Blood Flow & Metabolism 33, no. 8 (May 8, 2013): 1251–58. http://dx.doi.org/10.1038/jcbfm.2013.76.

Full text
Abstract:
Evidence indicates a critical role for cerebrovascular dysfunction in Alzheimer's disease (AD) pathophysiology. We have shown that fibrin(ogen), the principal blood-clotting protein, is deposited in the AD neurovasculature and interacts with beta-amyloid (Ab), resulting in increased formation of blood clots. As apolipoprotein E (ApoE), a lipid-transporting protein with three human isoforms (E2, E3, and E4), also binds to Aβ, we hypothesized that ApoE and fibrin(ogen) may have a combined effect on the vascular pathophysiology in AD. We assessed whether APOE genotype differentially influences vascular fibrin(ogen) deposition in postmortem brain tissue using immunohistochemistry. An increased deposition of fibrin(ogen) was observed in AD cases compared with non-demented controls, and there was a strong correlation between cerebral amyloid angiopathy (CAA) severity and fibrin(ogen) deposition. Moreover, brains from AD cases homozygous for APOE ε4 showed increased deposition of fibrin(ogen), specifically in CAA- and oligomeric Aβ-positive vessels compared with AD APOE ε2 and ε3 allele carriers, an effect that was not directly linked to CAA severity and cerebrovascular atherosclerosis. These data further support a role for fibrin(ogen) in AD pathophysiology and link the APOE ε4/ε4 genotype with increased thrombosis and/or impaired fibrinolysis in the human AD brain.
APA, Harvard, Vancouver, ISO, and other styles
8

Besli, Nail, and Guven Yenmis. "Assessment of the Interaction of Aggregatin Protein with Amyloid-Beta (Aβ) at the Molecular Level via In Silico Analysis." Acta Chimica Slovenica 67, no. 4 (December 15, 2020): 1262–72. http://dx.doi.org/10.17344/acsi.2020.6175.

Full text
Abstract:
Alzheimer’s disease is a major neurodegenerative illness whose prevalence is increasing worldwide but the molecular mechanism remains unclear. There is some scientific evidence that the molecular complexity of Alzheimer’s pathophysiology is associated with the formation of extracellular amyloid-beta plaques in the brain. A novel cross- phenotype association analysis of imaging genetics reported a brain atrophy susceptibility gene, namely FAM222A and the protein Aggregatin encoded by FAM222A interacts with amyloid-beta (Aβ)-peptide (1-42) through its N-terminal Aβ binding domain and facilitates Aβ aggregation. The function of Aggregatin protein is unknown, and its three-dimensional structure has not been analyzed experimentally yet. Our goal was to investigate the interaction of Aggregatin with Aβ in detail by in silico analysis, including the 3D structure prediction analysis of Aggregatin protein by homology modeling. Our analysis verified the interaction of the C-terminal domain of model protein with the N-terminal domain of Aβ. This is the first attempt to demonstrate the interaction of Aggregatin with the Aβ. These results confirmed in vitro and in vivo study reports claiming FAM222A helping to ease the aggregating of the Aβ-peptide.
APA, Harvard, Vancouver, ISO, and other styles
9

Katsinelos, Taxiarchis, Michael Doulberis, Stergios A. Polyzos, Apostolis Papaefthymiou, Panagiotis Katsinelos, and Jannis Kountouras. "Molecular Links Between Alzheimer's Disease and Gastrointestinal Microbiota: Emphasis on Helicobacter pylori Infection Involvement." Current Molecular Medicine 20, no. 1 (December 13, 2019): 3–12. http://dx.doi.org/10.2174/1566524019666190917125917.

Full text
Abstract:
Alzheimer's disease (AD) is a neurodegenerative disease and the main form of dementia, characterized by progressive cognitive decline and detrimental consequences in both personal-family and global level. Within this narrative review, we provide recent molecular aspects of Tau, a microtubule AD-associated protein, as well as amyloid beta, involved in AD pathophysiology. Moreover, we provide additional emerging data from basic research as well as clinical studies indicating an implicating role of gastrointestinal microbiota (GI-M), including Helicobacter pylori infection (Hp-I), in AD pathophysiology. Likewise, we identified through a molecular prism the current evidence of AD pathogenesis as well as its linkage with GI-M and emphasizing the role of Hp-I. All in all, additional large-scale studies are required for the further clarification of AD pathophysiology and its connection with GI-M and Hp-I, so as novel therapies on molecular basis become available.
APA, Harvard, Vancouver, ISO, and other styles
10

Kulas, Joshua A., Kendra L. Puig, and Colin K. Combs. "Amyloid precursor protein in pancreatic islets." Journal of Endocrinology 235, no. 1 (October 2017): 49–67. http://dx.doi.org/10.1530/joe-17-0122.

Full text
Abstract:
The amyloid precursor protein (APP) has been extensively investigated for its role in the production of amyloid beta (Aβ), a plaque-forming peptide in Alzheimer’s disease (AD). Epidemiological evidence suggests type 2 diabetes is a risk factor for AD. The pancreas is an essential regulator of blood glucose levels through the secretion of the hormones insulin and glucagon. Pancreatic dysfunction is a well-characterized consequence of type 1 and type 2 diabetes. In this study, we have examined the expression and processing of pancreatic APP to test the hypothesis that APP may play a role in pancreatic function and the pathophysiology of diabetes. Our data demonstrate the presence of APP within the pancreas, including pancreatic islets in both mouse and human samples. Additionally, we report that the APP/PS1 mouse model of AD overexpresses APP within pancreatic islets, although this did not result in detectable levels of Aβ. We compared whole pancreas and islet culture lysates by Western blot from C57BL/6 (WT), APP−/− and APP/PS1 mice and observed APP-dependent differences in the total protein levels of GLUT4, IDE and BACE2. Immunohistochemistry for BACE2 detected high levels in pancreatic α cells. Additionally, both mouse and human islets processed APP to release sAPP into cell culture media. Moreover, sAPP stimulated insulin but not glucagon secretion from islet cultures. We conclude that APP and its metabolites are capable of influencing the basic physiology of the pancreas, possibly through the release of sAPP acting in an autocrine or paracrine manner.
APA, Harvard, Vancouver, ISO, and other styles
More sources

Dissertations / Theses on the topic "Amyloid beta-protein Pathophysiology"

1

Flood, Fiona. "Alzheimer's disease-related amyloid precursor protein and presenilin genes : normal function and pathophysiology /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-050-8/.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Yu, Man-shan, and 余雯珊. "Molecular mechanisms of neuronal death in {221}-amyloid peptide toxicity: from basic science to translationalresearch." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38705941.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Kanyenda, Limbikani J. "The role of luteinising hormone (LH)/human chorionic gonadotropin (hCG) in regulating the production of beta amyloid (Aβ), a protein central to Alzheimer's disease (AD)." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2006. https://ro.ecu.edu.au/theses/358.

Full text
Abstract:
Alzheimer's disease (AD), a progressive neurodegenerative disorder of the brain, is the most common form of dementia among the elderly which is clinically characterised by memory complaints and personality changes. AD is classified broadly into early on set AD (EOAD, occurringyrs) and late on set (LOAD, occurring >65 yrs). Hormonal changes following menopause/andropause have been implicated in AD development and pathogenesis. Currently high levels of the gonadotropins LH and FSH have been associated with increased risk of AD development; however the exact role of LH in AD pathogenesis remains unknown. Interestingly LH and hCG have similar structure and function, thus effects of hCG on Aβ production were assessed in vivo and in vitro models. Additionally the link between pregnancy and cognitive function were also assed.
APA, Harvard, Vancouver, ISO, and other styles
4

Sarroukh, Rabia. "Etude de la structure et de la toxicité des oligomères du peptide amyloïde-beta: implication dans la maladie d'Alzheimer." Doctoral thesis, Universite Libre de Bruxelles, 2011. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209874.

Full text
Abstract:
La maladie d’Alzheimer est actuellement la forme de démence la plus courante. Les causes, les facteurs de risques ainsi que le(s) mécanisme(s) conduisant à l’apparition des symptômes ne sont pas encore clairement connus. Néanmoins, le rôle central du peptide amyloïde (Aβ) dans le développement de la maladie a été démontré au travers de nombreuses recherches et fait actuellement l’unanimité. L’espèce oligomérique d’Aβ est plus précisément pointée doigt comme l’espèce la plus toxique. La formation des oligomers, au cours du processus d’agrégation, conduit à une population hétérogène en termes de taille et morphologies limitant la compréhension actuelle de leur implication dans le processus pathologique ainsi que dans l’initiation de la maladie.

Notre étude structurale minutieuse du processus d’agrégation du peptide Aβ démontre la formation d’agrégats dont le degré d’assemblage augmente au cours du temps. Nous avons montré que les agrégats identifiés comme étant des oligomères adoptent une structure en feuillets β antiparallèles. Tandis que l’interconversion de la structure β d’antiparallèle à parallèle conduit à la formation de fibrilles. Sur base de l’interprétation des spectres infrarouges analysés par corrélation à 2 dimensions, nous suggérons que ce changement de conformation est rendu possible grâce aux modifications des liens hydrogènes. En effet, les liens hydrogènes intramoléculaires qui stabilisent la structure antiparallèle des brins β disparaissent en faveur de liens intermoléculaires conduisant à la formation de feuillets β parallèles. De plus, ce changement de conformation requière la rotation des brins β le long de leur axe respectif.

Notre travail a pu mettre en avant le rôle central des oligomères dans la pathologie d’une part par leur rôle d’intermédiaires transitoires nécessaires et obligatoires à la formation des fibrilles mais également par la relation étroite qui existe entre leur structure en feuillets β antiparallèles et leur toxicité cellulaire. La modulation et/ou suppression de cette conformation est requise spécifiquement pour réguler leur toxicité et empêcher le processus de mauvais reploiement du peptide conduisant au développement de la maladie.

Enfin, nous avons également apporté de nouvelles informations concernant l’implication des membranes biologiques dans le mécanisme de toxicité des oligomères. Nos résultats démontrent que l’interaction du peptide avec un modèle de la membrane biologique ne conduit pas à la déstabilisation de cette dernière. L’hypothèse suggérant la formation de pores et/ou de canaux ioniques comme mécanisme de cytotoxicité est de facto réfutée par notre travail. Néanmoins, nous suggérons que l’interaction du peptide avec les lipides modifie le processus d’agrégation décrit dans la première partie de notre travail. Elle accélère l’étape de nucléation permettant la formation rapide d’oligomères à la surface de la membrane et accentuant ainsi leur probabilité d’interaction avec les protéines membranaires neuronales telles que les récepteurs de neurotransmetteurs./

Aggregation of amyloid-β peptides (Aβ1-40 and Aβ1-42) leads to formation of heterogeneous

toxic species, oligomers and fibrils, implicated in Alzheimer’s disease. As oligomers were

identified as the most cytotoxic entities, our research did focus on their implications in

pathology and the Aβ aggregation process which are currently not fully understood.

Using ATR-FTIR spectroscopy, we demonstrated that Aβ oligomers adopt an antiparallel β-

sheet structure. β-sheet interconversion from antiparallel to parallel seems to be an important

step in the Aβ oligomers-to-fibrils transformation. Furthermore, 2-D correlation analysis of

infrared spectra recorded during aggregation showed that Aβ isoforms undergo different β-

sheet reorganizations explaining their distinct aggregation kinetics. Aβ1-40 misfolding seems

to be related to a greater extent of secondary structure changes (increase of β-sheet structure

while α-helices and random coil structures content decrease). On the contrary, the same

analysis for Aβ1-42 suggests that a possible β-strand ‘rotation’ triggering inter-H bonding

formation and stabilizing fibrils may probably explain the antiparallel to parallel β-sheet

conversion.

We also provided evidence that cytotoxicity is strongly related to the oligomeric antiparallel

β-sheet structure of Aβ. The concomitant absence of antiparallel β-sheet structure due to

incubation with whey protein-derived peptide hydrolysate strongly suggests that cytotoxicity

and β-sheets organization are related.

Formation of β-barrel spanning the lipid membrane has been proposed to explain this Aβ

structure-toxicity relationship. In the last part of our work, we demonstrated that the

interaction of Aβ1-42 with anionic lipid membranes creates and/or stabilizes specific-size

oligomers. These oligomers, especially the dodecamer, are known to be the most toxic.

Nevertheless, we could not show that these specific oligomers are implicated in membrane

destabilization. Further works are needed to separate and study the individual properties of

each oligomer.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished

APA, Harvard, Vancouver, ISO, and other styles
5

Qu, Xiaoyi. "Microtubule Dynamics in Tau-dependent Amyloid Beta Synaptotoxicity." Thesis, 2019. https://doi.org/10.7916/d8-4qaj-2923.

Full text
Abstract:
Alzheimer’s disease is the most common form of dementia among older adults, and directly contributes to the third leading cause of death in the United States. Although amyloid plaques and tau-loaded neurofibrillary tangles have been identified as the main pathological features of Alzheimer’s disease for more than one hundred years, the molecular mechanism is still poorly understood and treatments are limited to palliative care. Oligomeric Amyloid beta plays a crucial synaptotoxic role in Alzheimer’s disease, and hyperphosphorylated tau facilitates Amyloid beta toxicity, but the link between the two remains controversial. Since tau is a microtubule associated protein and microtubules are critical for neuronal functions, regulation of dynamic microtubules may serve as the link between Amyloid beta and tau. Here I propose a model in which Amyloid beta can induce changes in MT dynamics in dendrites and axons that are primary to tau hyperphosphorylation, while these MT changes are sufficient to cause tau hyperphosphorylation and necessary for Amyloid beta synaptotoxicity through tau. My thesis work further characterizes mammalian excitatory presynaptic boutons as hotspots for activity-dependent dynamic microtubule nucleation that is required for synaptic transmission during neuronal activation or Amyloid beta-induced neuronal injury through tau.
APA, Harvard, Vancouver, ISO, and other styles
6

Ramanan, Vijay K. "Pathways to dementia: genetic predictors of cognitive and brain imaging endophenotypes in Alzheimer's disease." Thesis, 2014. http://hdl.handle.net/1805/3797.

Full text
Abstract:
Indiana University-Purdue University Indianapolis (IUPUI)
Alzheimer's disease (AD) is a national priority, with nearly six million Americans affected at an annual cost of $200 billion and no available cure. A better understanding of the mechanisms underlying AD is crucial to combat its high and rising incidence and burdens. Most cases of AD are thought to have a complex etiology with numerous genetic and environmental factors influencing susceptibility. Recent genome-wide association studies (GWAS) have confirmed roles for several hypothesized genes and have discovered novel loci associated with disease risk. However, most GWAS-implicated genetic variants have displayed modest individual effects on disease risk and together leave substantial heritability and pathophysiology unexplained. As a result, new paradigms focusing on biological pathways have emerged, drawing on the hypothesis that complex diseases may be influenced by collective effects of multiple variants – of a variety of effect sizes, directions, and frequencies – within key biological pathways. A variety of tools have been developed for pathway-based statistical analysis of GWAS data, but consensus approaches have not been systematically determined. We critically review strategies for genetic pathway analysis, synthesizing extant concepts and methodologies to guide application and future development. We then apply pathway-based approaches to complement GWAS of key AD-related endophenotypes, focusing on two early, hallmark features of disease, episodic memory impairment and brain deposition of amyloid-β. Using GWAS and pathway analysis, we confirmed the association of APOE (apolipoprotein E) and discovered additional genetic modulators of memory functioning and amyloid-β deposition in AD, including pathways related to long-term potentiation, cell adhesion, inflammation, and NOTCH signaling. We also identified genetic associations to amyloid-β deposition that have classically been understood to mediate learning and memory, including the BCHE gene and signaling through the epidermal growth factor receptor. These findings validate the use of pathway analysis in complex diseases and illuminate novel genetic mechanisms of AD, including several pathways at the intersection of disease-related pathology and cognitive decline which represent targets for future studies. The complexity of the AD genetic architecture also suggests that biomarker and treatment strategies may require simultaneous targeting of multiple pathways to effectively combat disease onset and progression.
APA, Harvard, Vancouver, ISO, and other styles
7

Long, Justin M. "Novel regulation of neuronal genes implicated in Alzheimer disease by microRNA." Thesis, 2013. http://hdl.handle.net/1805/3758.

Full text
Abstract:
Indiana University-Purdue University Indianapolis (IUPUI)
Alzheimer disease (AD) results, in part, from the excess accumulation of the amyloid-β peptide (Aβ) as neuritic plaques in the brain. The short Aβ peptide is derived from a large transmembrane precursor protein, APP. Two different proteolytic enzymes, BACE1 and the gamma-secretase complex, are responsible for cleaving Aβ peptide from APP through an intricate processing pathway. Dysregulation of APP and BACE1 levels leading to excess Aβ deposition has been implicated in various forms of AD. Thus, a major goal in this dissertation was to discover novel regulatory pathways that control APP and BACE1 expression as a means to identify novel drug targets central to the Aβ-generating process. MicroRNAs (miRNA) are short, non-coding RNAs that act as post-transcriptional regulators of gene expression through specific interactions with target mRNAs. Global analyses predict that over sixty percent of human transcripts contain evolutionarily conserved miRNA target sites. Therefore, the specific hypothesis tested was that miRNA are relevant regulators of APP and BACE1 expression. In this work, several specific miRNA were identified that regulate APP protein expression (miR-101, miR-153 and miR-346) or BACE1 expression (miR-339-5p). These miRNAs mediated their post-transcriptional effects via interactions with specific target sites in the APP and BACE1 transcripts. Importantly, these miRNA also altered secretion of Aβ peptides in primary human fetal brain cultures. Surprisingly, miR-346 stimulated APP expression via target sites in the APP 5’-UTR. The mechanism of this effect appears to involve other RNA-binding proteins that bind to the APP 5’-UTR. Expression analyses demonstrated that these miRNAs are expressed to varying degrees in the human brain. Notably, miR-101, miR-153 and miR-339-5p are dysregulated in the AD brain at various stages of the disease. The work in this dissertation supports the hypothesis that miRNAs are important regulators of APP and BACE1 expression and are capable of altering Aβ homeostasis. Therefore, these miRNA may possibly serve as novel therapeutic targets for AD.
APA, Harvard, Vancouver, ISO, and other styles

Books on the topic "Amyloid beta-protein Pathophysiology"

1

Sipe, Jean D. Amyloid proteins: The beta sheet conformation and disease. Weinheim: Wiley-VCH, 2005.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
2

1924-, Kameyama Masakuni, ed. [Beta]-amyloid precursor proteins and neurotransmitter function: Proeedings of the eighth Workshop on Neurotransmitters and Diseases, Tokyo, June 1, 1991. Amsterdam, The Netherlands: Excerpta Medica, 1991.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
3

M, Nitsch Roger, and International Study Group on the Pharmacology of Memory Disorders Associated with Aging. Meeting, eds. Alzheimer's disease: Amyloid precursor proteins, signal transduction, and neuronal transplantation. New York, N.Y: New York Academy of Sciences, 1993.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
4

Chen, Shiouh-Yi. Neuropathology of beta-amyloid peptide (25-35). 1995.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
5

Conformational diseases - a compendium: Based on the first international workshop on conformational diseases. Jerusalem: Center for the Study of Emerging Diseases, 2001.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
6

L, Masters Colin, and Colloque médecine et recherche (9th : 1993 : Lyon, France), eds. Amyloid protein precursor in development, aging, and Alzheimer's disease. Berlin: Springer-Verlag, 1994.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
7

(Editor), K. Beyreuther, Y. Christen (Editor), and C. L. Masters (Editor), eds. Neurodegenerative Disorders: Loss of Function Through Gain of Function (Research and Perspectives in Alzheimer's Disease). Springer, 2001.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
8

Lee, V. M. Y., J. Q. Trojanowski, L. Buee, and Y. Christen. Fatal Attractions: Protein Aggregates in Neurodegenerative Disorders. Springer Berlin / Heidelberg, 2010.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
9

Lee, V. M. Y., J. Q. Trojanowski, L. Buee, and Y. Christen. Fatal Attractions: Protein Aggregates in Neurodegenerative Disorders. Springer London, Limited, 2013.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
10

V.M.-Y. Lee (Editor), J. Q. Trojanowski (Editor), L. Buee (Editor), and Y. Christen (Editor), eds. Fatal Attractions: Protein Aggregates in Neurodegenerative Disorders (Research and Perspectives in Alzheimer's Disease). Springer, 2000.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
More sources

Book chapters on the topic "Amyloid beta-protein Pathophysiology"

1

Díaz, Mario, and Raquel Marin. "Lipid Rafts and Development of Alzheimer’s Disease." In Cerebral and Cerebellar Cortex – Interaction and Dynamics in Health and Disease. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.94608.

Full text
Abstract:
A wealth of evidence accumulated over the last two decades has unambiguously linked lipid rafts to neurodegenerative diseases, in particular to Alzheimer’s disease (AD). These microdomains are highly dynamic membrane platforms with differentiated physicochemical and molecular properties compared to the surrounding membrane microenvironment, and are the locus for a number of central processes in neuronal physiology. Most recent evidence pinpoint to lipid rafts as main players in AD neuropathology. It is now widely accepted that lipid rafts actively participate in the processing of amyloid precursor protein to generate amyloid beta peptides, a main component of amyloid plaques. Current evidence have highlighted the existence of severe alterations in the molecular structure and functionality of lipid rafts in the frontal cortex of human brains affected by Alzheimer’s disease. An exceptionally interesting observation is that lipid raft destabilization can be demonstrated even at the earliest stages of AD neuropathology. In the present review, we will first elaborate on the structure and function of these multifaceted subcellular structures and second to focus on the impact of their alterations in neuronal pathophysiology along the onset and progression of AD continuum.
APA, Harvard, Vancouver, ISO, and other styles

Conference papers on the topic "Amyloid beta-protein Pathophysiology"

1

Senhorinha, Gláucia Maria, Arlys Emanuel Mendes da Silva Santos, and Douglas Daniel Dophine. "The role of metabolic syndrome in Alzheimer’s disease." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.319.

Full text
Abstract:
Background: Metabolic syndrome (MS) leads to the deposits formation of insoluble protein aggregates, neuroinflammation, oxidative stress, neuronal insulin resistance, progressive insulin resistance, desensitization and β-amyloid amyloidosis in the brain, besides direct ischemic effects which are closely associated with Alzheimer’s disease (AD).1 Objectives: The present study seeks to understand the role of the metabolic syndrome in the pathophysiology of Alzheimer’s disease and to describe preventive and therapeutic interventions. Methods: PUBMED and Web of Science were the databases used, the following descriptors were used to search the articles: “Alzheimer Disease” OR “Alzheimer Dementia” AND “Metabolic Syndrome”. Results: The studies in general have shown that MS is related to AD through brain insulin resistance, triggered by oxidative stress and neuroinflammation. It is related to the progressive atrophy of brain regions involved in the progression of AD. Insulin resistance in the brain is related to the progressive atrophy of the brain regions from initial progression of AD. These regions are cingulate cortices, medial temporal lobe, prefrontal gyri and other regions.³ Thus, there is an inhibition of the mechanisms of beta-amyloid removal, leading to its accumulation, which generates neuroinflammation, that in turn potentiates insulin resistance in the central nervous system, contributing to the genesis and progression of cognitive damage.2,3 Conclusions: Insulin resistance plays a major role in the initiation and perpetuation of cognitive impairment in AD. Furthermore, the components of the MS associated with AD, when treated with preventive and therapeutic measures, break this association by promoting rebalancing of the metabolism.
APA, Harvard, Vancouver, ISO, and other styles
You might also be interested in the extended bibliographies on the topic 'Amyloid beta-protein Pathophysiology' for particular source types:
Journal articles Books
We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!

To the bibliography