Thèses sur le sujet « ApoE- »
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Dinkel, Regina Elke. « In-vivo Metabolismus der VLDL-Apolipoproteine ApoB, ApoCIII und ApoE ». Diss., lmu, 2002. http://nbn-resolving.de/urn:nbn:de:bvb:19-3562.
Texte intégralReverté, Soler Ingrid. « Neurobehavioural effects associated with postnatal exposure to decabromodiphenyl ether in apoe2, apoe3 and apoe4 transgenic mice ». Doctoral thesis, Universitat Rovira i Virgili, 2012. http://hdl.handle.net/10803/76782.
Texte intégralDecabromodiphenyl Ether (BDE-209) is a flame retardant widely used and source of concern because ofthe toxicity showed by other Polibrominateddiphenyl ethers (PBDEs). The presenceof PBDEs in human’s breast milkmakes worrying its exposure during development. We hypothesised that an early exposure to BDE-209 can induce long-term impairments and interact with genetic factors, such as ApolipoproteinE genotype. Mice carrying the different Human ApoE isoforms treated with an acute oral dose of 0, 10 or 30 mg/kg of BDE-209 on postnatal day 10 were assessed for neurobehaviourduring development, in young adulthood and old age. BDE-209 exposure inducesadelay in physic and neuromotordevelopment and in myelin compaction in ApoE2 mice, decreases the levels of free thyroxin in adult femalesand decreases activity in ApoE4 mice. The most consistent effects across the lifespan are observed in ApoE3 mice and consist of impaired learning at 4 months, and impaired learning and memory and increased anxiety at 12 months.
Cambon, Karine. « Influence of ApoE polymorphism on synaptic morphometry during aging in the dentate gyrus of ApoE knockout and human ApoE transgenic mice ». Thesis, [n.p.], 2000. http://oro.open.ac.uk/19118/.
Texte intégralLundbäck, Daniel. « Alkoholkonsumtion och episodiskt minne.Kan APOE genen vid olika konsumtionsnivåer ha betydelse ? » Thesis, Stockholms universitet, Psykologiska institutionen, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-88448.
Texte intégralBetula
Hua, Jennifer. « Rôle des récepteurs P2X4 dans la dégradation d’ApoE : implication dans la maladie d’Alzheimer ». Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTT021/document.
Texte intégralP2X4 receptors (P2X4R) are purinergic ion channels expressed on neurons and microglia inthe central nervous system. They have been widely studied and have been implicated in manyphysiological and pathological processes. Previous studies conducted in the laboratoryrevealed an interaction between P2X4R and the Apolipoprotein E (ApoE), as well as anincrease in ApoE level in primary macrophages and microglia obtained from mice lackingP2X4R. Based on these results, this thesis aimed to decipher the mechanisms underlyingP2X4R regulation of ApoE levels. In addition, ApoE being a major risk factor forAlzheimer’s disease, part of this work investigated potential implications of P2X4R in thispathology.Results show that P2X4R modulates cathepsin B activity, which in turn promotes ApoElysosomal degradation. APP/PS1 mice lacking P2X4R show an increase in cognitiveperformances, a decrease in soluble Aβ peptide and an increase of microglia ApoE level.These results support that P2X4R modulates ApoE degradation in a cathepsin B-dependantmanner and that its invalidation leads to an improvement in Alzheimer’s pathology
Wassef, Hanny. « Synthesis and secretion of apoC-I and apoE by human SW872 liposarcoma cells ». Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82447.
Texte intégralSleiman, Lyne. « The Role of cIAP2 in Early and Late Atherosclerosis Lesion Development ». Thesis, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/20226.
Texte intégralD'EUGENIO, Ottavio. « VALUTAZIONE DI FATTORI DI RISCHIO GENETICI SU BASE POLIMORFICA NELLA MALATTIA DI ALZHEIMER ». Doctoral thesis, La Sapienza, 2006. http://hdl.handle.net/11573/917163.
Texte intégralEvans, Vanessa. « Intramuscular gene transfer of apolipoprotein E (ApoE) to reverse hyperlipidaemia and atherosclerosis in ApoE-deficient mice ». Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1444704/.
Texte intégralRantsi, P. (Petra). « Apoe 4-alleelien rooli saamelaisväestön muistisairauksissa ». University of Oulu, 2017. http://urn.fi/URN:NBN:fi:oulu-201711083079.
Texte intégralCarvalho, Liliana Patrícia Rodrigues de. « Genetic profiling of ApoE in dementia ». Master's thesis, Universidade de Aveiro, 2012. http://hdl.handle.net/10773/10720.
Texte intégralA demência é uma das principais causas de incapacidade entre os idosos, afetando mais de 36 milhões de pessoas em todo o mundo. É caracterizada pela deterioração progressiva das funções cognitivas, resultando em dificuldades no desempenho das atividades diárias do indivíduo. A idade de aparecimento dos sintomas, bem como a sua taxa de progressão, são variáveis entre a maior parte das demências, sendo estas geralmente caracterizadas por uma natureza progressiva, aumentando de gravidade ao longo do tempo. Entre os tipos mais frequentes de demência encontram-se a Doença de Alzheimer (DA), Demência Vascular, Demência de Corpos de Lewy e Demência Frontotemporal. O diagnóstico diferencial das demências é realizado tipicamente por testes neuro-psicológicos (para a exclusão de outras demências) e por exames imagiológicos. Contudo, muitos dos sintomas clínicos característicos podem sobrepor-se entre os diversos tipos de demência, o que pode constituir um problema devido a falta de especificidade e erros de diagnóstico. A compreensão dos fatores de risco ambientais e genéticos que podem modular o aparecimento e/ou progressão de doenças abre novas perspetivas relativamente à gestão destas neuropatologias. O gene da apolipoproteína E (ApoE) é reconhecido como o maior fator de risco na demência, desempenhando um papel central em particular no desenvolvimento da DA, sendo que os portadores do alelo ε4 são mais suscetíveis para a doença. Além disso, possíveis associações foram também propostas entre este gene e outras doenças neurológicas, sendo no entanto estes dados ainda controversos. Assim, o objetivo principal deste trabalho consistiu em determinar as frequências alélicas e genotípicas do gene ApoE num grupo de estudo piloto de pacientes com demência na região de Aveiro. Este grupo foi subdividido com base no diagnóstico neuroquímico, no qual foram avaliados os níveis de Aβ1-42, Tau-total e fosfo-Tau 181 no líquido cefalorraquidiano dos pacientes. Como resultado, observou-se que o alelo ε3 foi o mais frequente no grupo total, independentemente do tipo de patologia, e que o alelo ε2 foi o menos comum. O alelo ε4 foi de facto mais frequente em pacientes com DA do que em pacientes com outras neuropatologias, o que está de acordo com a relação proposta por outros autores. Adicionalmente, foi possível verificar que a frequência deste alelo nos pacientes com patologia amilóide é semelhante à observada no grupo DA, sugerindo um papel relevante para o ApoE no metabolismo e acumulação cerebral do Aβ. Consequentemente, estes indivíduos podem ter uma maior suscetibilidade para o desenvolvimento de DA no futuro. Deste modo, os nossos dados corroboram a ideia de que o alelo ε4 é um forte fator de risco para a DA e que deve ser considerado como um teste genético relevante que pode contribuir para o diagnóstico clínico da demência.
Dementia is one of the leading causes of disability among the elderly, affecting over 36 million people worldwide. It is characterized by progressive deterioration in cognitive functions that impair the successful performance of daily living activities. Most forms of dementia are progressive in nature, increasing in severity over time, with the rate of symptoms progression and the age at onset differing among the major dementing disorders. The most frequent types of dementia include Alzheimer´s Disease (AD), Vascular Dementia, Dementia of Lewy bodies and Frontotemporal Dementia. Differential diagnosis of dementia is typically done by neuropsychological testing (for exclusion of other dementias) and neuroimaging investigations. However, many of the clinical symptoms typical of dementia may overlap across dementia subtypes, which may constitute a diagnosis problem leading to lack of specificity and misdiagnosis. Understanding the environmental and genetic factors that modulate risks and outcomes of diseases can open new perspectives on the management of these neurological disorders. Apolipoprotein E gene (ApoE) is recognized as the major genetic risk factor in dementia, in particular playing a central role in AD development, being that ApoE allele ε4 carriers are more susceptible to disease. Furthermore, putative associations have also been proposed between this gene and other neurological disorders, nonetheless controversial data have been reported regarding these aspect. Hence, the aim of this work was to determine ApoE genotypic and allelic frequencies in a pilot study group of dementing patients from the catchment area of the “Hospital de São Sebastião” in “Santa Maria da Feira”. This group was subdivided according to their neurochemical-based diagnosis of dementia, in which Aβ1-42, phospho-Tau 181 and total-Tau levels in patients’ cerebrospinal fluid were evaluated. In this study, we could observe that allele ε3 was the most frequent in the total study group, independent of the type of pathology, and that allele ε2 was the less frequent. Allele ε4 was in fact more frequent in AD patients than in other neurological disease patients, in agreement with the proposed link established by other authors. Additionally, we also find that allele ε4 frequency in patients suffering from amyloid pathology is similar to that observed in AD group, suggesting a role for ApoE in Aβ metabolism and brain accumulation. Potentially, these patients have a higher susceptibility to develop AD pathology in the future. Thus, our data supports the idea that ApoE allele ε4 is a strong risk factor for AD development and that it may be considered as a relevant genetic test that may assist in the clinical diagnosis of dementia.
Wong, Clement Cheuk Man. « Plasma Apolipoprotein E Concentration In Type 2 Diabetes ». Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/20997.
Texte intégralROSSI, K. B. « Participação da Apolipoproteína-e na Atividade Microbicida in Vitro Contra o Mycobacterium Tuberculosis ». Universidade Federal do Espírito Santo, 2014. http://repositorio.ufes.br/handle/10/4582.
Texte intégralA parede celular de Mycobacterium tuberculosis (Mtb) é constituída por 60% de lipídios, impedindo a passagem de uma grande quantidade de substâncias, além de desempenhar um importante papel na munopatogênese. A apresentação desses antígenos aos linfócitos se dá por meio de moléculas do tipo CD1. Por sua vez a Apolipoproteína-E (ApoE), glicoproteína amplamente distribuída nos tecidos, pode facilitar a apresentação de lipídios pelo CD1. A ApoE possui três principais alelos ApoE- 2, 3 e 4, que codificam três isoformas de proteínas, tipos 2, 3 e 4, que possuem diferentes estruturas e funções. A presença de determinadas isoformas da ApoE está associada a doenças infecciosas, como herpes labial, dano hepático severo causado pelo vírus da hepatite C, diarréia infantil e tuberculose pulmonar. Neste contexto, avaliamos a participação da ApoE na atividade microbicida in vitro frente ao Mtb. Para tanto, foram arrolados 13 indivíduos PPD-, 17 indivíduos PPD+ e 4 indivíduos com tuberculose pulmonar ativa. O uso de plasma humano depletado de ApoE nos experimentos de atividade microbicida in vitro mostraram um aumento significante (p=0,02) no número de micobactérias (431.5 ± 81.92 UFC) quando comparado ao grupo controle (313.0 ± 74.61 UFC). Esses resultados foram confirmados por um modelo experimental utilizando esplenócitos de camundongos de camundongos C57BL/6 (815.9 ± 76.32 UFC) e animais APOE nocaute (1133 ± 86.85 UFC) (p= 0.021). Quanto à produção de IL-10, no grupo PPD+, observamos que o grupo com depleção de ApoE (866.7 ± 447.8) apresentou uma produção menor desta citocina com relação ao controle infectado (1089 ± 481.3) (p=0,023). Já em relação ao IFN-, em ambos os grupos observou-se, após 72 horas, uma tendência à diminuição da produção dessa citocina no grupo com depleção, com relação ao grupo controle. Esses dados sugerem que a ApoE tem papel distinto na ativação da resposta imune e sua ausência pode prejudicar a resposta imune frente à tuberculose.
Stening, Eva. « The Influence of APOE ε4 on the Hippocampus and Hippocampus-Dependent Memory ». Doctoral thesis, Uppsala universitet, Institutionen för psykologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-302855.
Texte intégralElam, Kit. « MEMORY AND DEFAULT NETWORK ACTIVATION AS A FUNCTION OF APOE GENOTYPE ». OpenSIUC, 2010. https://opensiuc.lib.siu.edu/dissertations/204.
Texte intégralDamy, Sueli Blanes. « Associação entre infecção experimental por Mycoplasma pneumoniae e/ou Chlamydophila (Chlamydia) pneumoniae e a intensidade das lesões ateroscleróticas da aorta, em camundongos C57BL/6 apoE KO, com ênfase na diferença entre os sexos ». Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/10/10133/tde-16042007-121022/.
Texte intégralIndependent of the presence or not a favorable ambient, mechanisms by which infectious agents may boost atherogenesis and clinical aspects are not fully elucidated. In spite of many demonstrations of infeccious agent antigens or DNA, the question if the infection may iniciate or aggravate the atherosclerotic process remains unanswered, requiring further studies. Therefore, the present work studies if the experimental infection of C57BL/6 apoE KO mice by C. pneumoniae and/or M. pneumoniae induces or affects the intensity of atherosclerosis and its characteristics of plaque vulnerability, with regard to the gender and/or the cholesterolrich diet. Methods: a group of mice was fed with 1% cholesterol-enriched diet (hyperlipidemic), from two months of age; the other group received adequately formulated food for the species (normolipidemic). At eight months of age, the mice were subgrouped according to inoculation intra-peritoneally with 106 IFU of C. pneumoniae and/or 106 CFU of M. pneumoniae, and re-inoculation one month later. They were killed at ten months of age. Cross-sectional thoracic aorta fragments were studied in embedded in paraffin block sections stained Hematoxylin-eosin and Masson?s trichromic techniques. Differences in the median of the variables: plaque height, plaque area, area of fat plaque, luminal area and percent obstruction of the lumen searched using the Mann Whitney?s test, with a 5% level of rejection. Results: the infection by C. pneumoniae and/or M. pneumoniae worsened atherosclerosis in both males and females C57BL/6 apoE KO mice. However, the M. pneumoniae inoculated female group presented more unstable plaques represented by positive remodeling of the vessel. The co-infection by both bacteria induced more stable plaque represented by low fat content and absence of vessel remodeling, in both male and female mice. The introduction of cholesterol enriched diet led to lack of positive vessel remodeling in M.pneumoniae inoculated female group, but development of unstable plaques characterized by large plaque are with high content of fat, in co-infected ones. In male groups there was development of plaque with higher fat content in the subgroup inoculated with C.pneumoniae. Conclusion: Infection by M. pneumoniae and/or C. pneumoniae, in C57BL/6 apoE KO mice, led to development or aggravation of atherosclerotic plaques, with differences regarding intensity and pattern of vulnerability according to the gender versus type of infectious agents. The infected female groups presented more aggravation of atherosclerosis than male ones. Cholesterol enriched diet aggravated the intensity of atherosclerosis and changed the patterns of vulnerability of infected subgroups.
DAL, MAGRO ROBERTA. « Enhanced brain targeting of ApoE-functionalized lipid nanoparticles ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2016. http://hdl.handle.net/10281/103191.
Texte intégralMartinic, Goran (Gary), of Western Sydney Hawkesbury University, of Science Technology and Environment College et School of Environment and Agriculture. « Cyclodextrins as potential human anti-atherosclerotic agents ». THESIS_CSTE_EAG_Martinic_G.xml, 2001. http://handle.uws.edu.au:8081/1959.7/129.
Texte intégralMaster of Science (Hons)
Hussain, Aseem. « Beneficial effects of estradiol are mediated through apoE / ». View online, 2008. http://repository.eiu.edu/theses/docs/32211131425346.pdf.
Texte intégralTrachtenberg, Aaron J. « The effects of APOE genotype on brain function ». Thesis, University of Oxford, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.542982.
Texte intégralXie, Ting. « Interactions épistatiques et modifications épigénétiques pour la stratification moléculaire des maladies chroniques ». Thesis, Université de Lorraine, 2017. http://www.theses.fr/2017LORR0339/document.
Texte intégralChronic diseases, like cardiovascular diseases (CVD), Alzheimer’s disease (AD), depression and osteoporosis, are major causes of mortality in the world. Identification of common to those diseases risk factors could help for a better-monitored ‘healthy’ aging, by promotion of personalised strategies for risk prediction, early prevention and adequate treatment, all taking into account the very often existing comorbidities. In this thesis, 8 publications have been developed. Initially, in a review paper, I have summarised the current challenges and opportunities of pharmacogenomics of CVD medications. I have participated in the formation of an international consortium, the VEGF Consortium, and I have participated in a study that identified significant epistatic interactions between polymorphisms that regulate the levels of VEGF and their effects on blood pressure and adiposity indexes. I have also demonstrated that one genetic marker of VEGF, rs4416670, was significantly associated with an increased risk for depression. Furthermore, I have reported two significant interactions between VEGF-related variants affecting the femoral neck bone mineral density in post-menopausal women. I have focused also on two markers linked with lipids metabolism: the apolipoprotein E (APOE) and the lipolysis-stimulated receptor (LSR). I have found that the LSR variant rs916147 can interact with APOE in a way that reverses the protective effect of the ε2 allele of APOE on blood lipids, thus providing new insights in the mechanisms underlying type III hyperlipoproteinemia. Epistatic interactions between these two genes have also been shown to increase the risk of AD, even in the absence of the known risk allele APOE ε4. Finally, I have performed epigenome-wide association studies (EWAS) on central obesity and blood lipid traits in healthy individuals. The results suggest that one methylation probe could affect waist circumference through an insulin-signaling pathway. Furthermore, two methylations probes were associated with triglycerides levels through genes linked with genetic heart diseases (PRKAG2) and with inhibition of the Wnt/beta-catenin signaling that is involved in CVD and AD development (KREMEN2). In conclusion, this thesis used the study of epistasis and epigenetics and identified complex inter-relationships between VEGF, LSR, APOE and different chronic diseases (CVD, AD, osteoporosis, depression) and novel mechanisms that link disease development with DNA methylation, thus demonstrating their role as common denominators of diseases that can be used as valuable markers in personalised medicine
Nielsen, Henrietta M., Kewei Chen, Wendy Lee, Yinghua Chen, Robert J. Bauer, Eric Reiman, Richard Caselli et Guojun Bu. « Peripheral apoE isoform levels in cognitively normal APOE ε3/ε4 individuals are associated with regional gray matter volume and cerebral glucose metabolism ». BIOMED CENTRAL LTD, 2017. http://hdl.handle.net/10150/622812.
Texte intégralGARCIA, Analia Nusya de Medeiros. « Polimorfismos dos genes CYP 46 e APOE e declínio cognitivo em idosos residentes no distrito de Fernando de Noronha-PE ». Universidade Federal de Pernambuco, 2011. https://repositorio.ufpe.br/handle/123456789/8317.
Texte intégralO Declínio Cognitivo Leve (DCL) é um estado mental considerado a zona de transição entre o envelhecimento normal e a fase mais inicial de demência, sendo uma fase importante para a precocidade diagnóstica. Nos últimos anos, pesquisas estão sendo desenvolvidas na busca de marcadores genéticos para esta zona de pré-demência, como os polimorfismos dos genes da apolipoproteína E (APOE) representada por 3 alelos (E2, E3, E4) e do colesterol 24S-hidroxilase (CYP46) com alelos T e C. Indivíduos portadores do APOE E4 tem fator de risco quatro vezes maior de desenvolver a Demência de Alzheimer e dez vezes mais probabilidade se tiver associado os polimorfismos dos genes APOE e CYP46. O objetivo deste estudo foi investigar a possível associação entre o polimorfismo dos genes CYP46(T/C), APOE E4 e a presença de DCL na população idosa do Distrito de Fernando de Noronha, totalizando uma seleção de 52 indivíduos. A avaliação clínica foi realizada através de exame físico, funcional e mental. Foram aplicados testes neuropsiquiátricos (Mini Exame do Estado Mental, Teste de Fluência Verbal, Teste do Relógio) e a identificação do genótipo dos polimorfismos do APOE e CYP46 pelo método de PCR-RFLP. Como resultados observou-se que 87% da amostra apresentou declínio cognitivo leve. No Mini Exame do Estado Mental, Teste de Fluência Verbal e Teste do Relógio foi observado declínio cognitivo em 42,8%, 31,9% e 53,2% respectivamente. Foi observada uma frequência alélica de 10% para o alelo E4. Não foi observada associação entre APOE E4 e declínio cognitivo. Os alelos T (p = 0,628) e C (p = 0,2076) do gene Cyp46 não estão associadas ao DCL na população estudada. Não foi observada associação (p = 0,4286), quando analisado o sinergismo entre o polimorfismo dos genes Cyp46(T/C) e APOE E4 no desenvolvimento do DCL. Nesta população, os resultados sugerem que os polimorfismos dos genes Cyp46(T/C) e APOE E4 não estão associados ao DCL
Coppens, Ryan Patrick. « ApoE4 Genotype as a Moderator of Brain Responses to Target Stimuli Prior and Subsequent to Smoking Abstinence ». OpenSIUC, 2017. https://opensiuc.lib.siu.edu/dissertations/1494.
Texte intégralFerguson, Chantal M. « Modulating ApoE with Tissue Specific siRNAs in Alzheimer’s Disease ». eScholarship@UMMS, 2021. https://escholarship.umassmed.edu/gsbs_diss/1132.
Texte intégralSinclair, Lindsey Isla. « Molecular and life-course aspects of APOE in cognition ». Thesis, University of Bristol, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.701968.
Texte intégralBlanchard, Valentin. « Approches biochimique, épidémiologique et clinique du métabolisme intégré de la Lipoprotéine (a) ». Thesis, La Réunion, 2020. http://www.theses.fr/2020LARE0007.
Texte intégralOne in five individuals in the population displays elevated circulating levels of lipoprotein (a) [Lp(a)], a highly atherogenic lipoprotein resembling LDL. Pathophysiological, epidemiological and genetic studies demonstrate that circulating Lp(a) levels above 125 nmol/L are associated with a sharp increase in cardiovascular events rate.The major structural difference between Lp(a) and LDL is that Lp(a) contains a signature protein, apo(a), extremely polymorphic in size as it contains 1 to more than 40 Kringle IV2 (KIV2) domains. The size of apo(a) is inversely correlated with the circulating levels of Lp(a). Besides apo(a), apoE and PCSK9 are the only other plasma proteins known to modulate Lp(a) levels. The aims of my PhD project were to assess how the size of apo(a), the polymorphism of apoE and the pharmacological inhibition of PCSK9 govern Lp(a) plasma concentrations. First, we have developed a robust methodological approach to quantitatively assay apolipoproteins, assess their polymorphisms and evaluate their metabolic fluxes by mass spectrometry. In addition, we have set up a resolutive separation technique allowing the investigation of distinct apo(a) isoforms on agarose gels. We then showed using mass spectrometry that apoE specifically present on VLDL impacts on Lp(a) production, synthesis and/or assembly. In addition, we clearly established that familial hypercholesterolemic patients specifically carrying the apoE2 isoform display reduced Lp(a) plasma levels and are thereby less prone to recurrent cardiovascular events compared with apoE3 or E4 carriers. Finally, we demonstrate that the response to PCSK9 inhibitor treatments of patients at high cardiovascular risk in terms of Lp(a) lowering is proportional to the size of apo(a). We also observed that apheresis procedures performed on a patient with extreme Lp(a) plasma levels reduce his risk of undergoing recurrent myocardial infarction. Taken together, my PhD results allowed us to decipher the physiological modalities by which apo(a) size and apoE polymorphism modulate the circulating levels of this extremely atherogenic lipoprotein species. The therapies currently available (PCSK9 inhibitors, plasmapheresis) remain however clearly insufficient to treat patients with elevated Lp(a)
Szostak, Justyna. « Activité physique et prévention de l'arthérosclérose : Mise en évidence de l’implication des PPAR (Peroxisome Prolife- raor-Activated Receptor) dans la cardioprotection induite par l’exercice physique soumis ou volontaire chez la souris ApoE-/- mice ». Thesis, Besançon, 2012. http://www.theses.fr/2012BESA3006/document.
Texte intégralAtherosclerosis is a complex inflammatory process, leading cause of morbidity and mortality in France.Inflammation is essential in initiation, progression and atherosclerosis plaque destabilization leading to acutecardiovascular events. Recent studies suggest that pharmacological PPAR activation prevents ATH developpementand progression and decreased cardiovascular mortality. Compared to pharmacological treatment,physical exercise also significantly prevents cardiovascular mortality.The aim of the first study was to investigate the influence of physical exercise on ATS development andPPAR expression in arterial wall. Our results had shown that physical exercise decrease ATH progressionand increase PPAR-γ expression in arterial wall. Interestingly, PPAR-γ inhibition with BADGE, a PPAR-γantagonist abolishes these antiatherogenic effects. Hypertension increase ATH complication such as plaque rupture. The aim of the second study were to investigatePPAR-γ implication in progression and stabilization of ATH lesions in hypercholesterolemic and hypertensiveApoE-/- mice (2K1C) submitted to different exercises (voluntary wheel running and submitted treadmillrunning) or treated with telmisartan an anti-hypertensive drug. Our results shown that, physical exerciseprevents ATS cardiovascular events by several mechanisms. Similarly to telmisartan, physical exercisesstabilize ATH lesion. Moreover results shown that, submitted exercise and telmisartan have an comparablemechanism. In fact, they significantly decrease pro-inflammatory cytokines expression and in the same timeactivated PPAR-γ expression in arterial wall. Contrary to submitted exercise, voluntary exercises increasesexpression of anti-inflammatory cytokines IL-1ra and increase M2 marker CD206. These results suggestthat voluntary and submitted exercise have two different mechanism of action. Moreover, M2 surexpressionin response to voluntary exercise shift the inflammatory balance in favor to M2. Further, this change of balancein favor to M2, is significantly correlated to decrease of ATH progression. Voluntary exercises significantlydecreases ATH progression in the same levels like telmisartan treatment.Voluntary and submitted exercise has two different mechanisms, submitted exercise decrease proinflammatory
Cieslak, Stephen Gerard. « The Effects of L-Cysteine on Alzheimer's Disease Pathology in APOE2, APOE3, and APOE4 Homozygous Mice ». BYU ScholarsArchive, 2016. https://scholarsarchive.byu.edu/etd/6585.
Texte intégralBouchareychas, Laura. « Implication des phagocytes mononuclées dans l'évolution de la plaque d'athérosclérose et relation avec l'homéostasie du cholestérol et des lipoprotéines ». Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066282/document.
Texte intégralAtherosclerosis represents a chronic pathophysiological process implicated in the majority of cardiovascular diseases. The development of atherosclerotic lesions is characterized by an accumulation of extra and intracellular lipids in the arterial wall at the origin of a strong inflammatory response involving macrophages.Macrophages are considered key actors in the development of atherosclerotic plaques. Indeed, because of their ability to metabolize cholesterol (capture, storage, efflux), to regulate inflammation and to phagocyte apoptotic cells, they exert pro and/or anti-atherogenic functions that may be modulated therapeutically. In this context, we evaluated the therapeutic potential of macrophages protected against apoptosis, on the progression of established atherosclerotic lesions.We have demonstrated that increased macrophage survival can slow down the progression of established lesions, stabilize lesion and reduce cholesterol levels. These athero-protective effects are attributed to the increase in Kupffer cells and Ly-6Clow monocytes partly due to their ability to produce apolipoprotein E. We also show that Kupffer cells are involved in the clearance of pro-atherogenic lipoproteins. The increase in ApoE pool and in Kupffer cells reduces cholesterol levels and thus lesion progression
McCorkindale, Andrew Neil. « Investigating the pathogenesis of Alzheimer’s disease with machine learning ». Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29764.
Texte intégralHaskett, Darren. « Progressive Alterations in Microstructural Organization and Biomechanical Response in the ApoE Mouse Model of Aneurysm and the Underlying Changes in Biochemistry ». Diss., The University of Arizona, 2015. http://hdl.handle.net/10150/581126.
Texte intégralCAMPOREZ, D. « BIOMARCADORES de Diagnóstico Complementar na Doença de Alzheimer : Enfoque em Genes Que Participam da Formação da Placa Beta-amiloide,via do Folato e Geração de Estresse Oxidativo ». Universidade Federal do Espírito Santo, 2018. http://repositorio.ufes.br/handle/10/7147.
Texte intégralA doença de Alzheimer (DA), é o tipo mais comum de demência relacionada a idade. É uma doença neurodegenerativa crônica, grave, progressiva, associada à perda de memória e cognição, que pode levar à morte. O maior fator de risco para o desenvolvimento da doença é a idade avançada, com uma complexa interação de fatores ambientais e genéticos que juntos podem aumentar a incidência da doença. Ainda que sua causa seja desconhecida, os fatores genéticos e o estresse oxidativo desempenham um papel importante na patogênese da DA. Neste estudo de associação nós investigamos se polimorfismos nos genes APOE (rs429358 e rs7412), FOXO3 (rs2802292), MTHFD1L (rs11754661), SERPINA3 (rs4934), SIRT1 (rs2273773) e SOD2 (rs4880) e fatores ambientais como: nível educacional, etnia e gênero estão associados com risco para a DA em uma amostra de 332 indivíduos idosos do sudeste brasileiro (109 pacientes com diagnóstico provável de DA e 223 controles - idosos saudáveis pareados por idade e gênero). Os polimorfismos genéticos foram analisados por meio da reação em cadeia da polimerase em tempo real (PCR-RT). Na nossa amostra o polimorfismo do gene APOE mostrou estar altamente associado com a doença, tendo os genótipos Ɛ4Ɛ4 e Ɛ3Ɛ3 demonstrado serem fator de risco e proteção, respectivamente. O genótipo GG do gene MTHFD1L mostrou estar associado com o aumento do risco de desenvolver a doença de Alzheimer. Já o genótipo GG e AG do gene SERPINA3 demonstraram ser fatores de proteção e risco, respectivamente. O genótipo TT e CT do gene SIRT1 também mostraram correlação com a doença. O nível educacional mostrou estar associado positivamente para os indivíduos do grupo controle que tiveram uma educação formal por mais de quatro anos. Os polimorfismos FOXO3 e SOD2 não demonstraram estar associados com a amostra e a doença em questão. Nossos resultados corroboram outras pesquisas, que demonstram que a etiologia da DA pode estar envolvida com alterações na via do folato, com o aumento do estresse oxidativo nas células do sistema nervoso central, além de apoiar a participação de proteínas formadoras das placas beta-amiloides na patologia da DA. Esses resultados podem ser úteis na busca de biomarcadores genéticos precoces capazes de identificar os sintomas do surgimento da demência, e fornecer novos dados para terapias no futuro, ajudando no entendimento deste distúrbio. Além disso, reforçam a hipótese de que diversos genes estão envolvidos na etiologia da DA, uma condição caracterizada também por instabilidade genômica e estresse oxidativo elevados, que podem contribuir significativamente para a degeneração neurológica observada nos pacientes.
Li, Xiaojing. « Relating Brain Signal Complexity, Cognitive Performance and APOE Polymorphism – the Case of Young Healthy Adults ». Doctoral thesis, Humboldt-Universität zu Berlin, 2020. http://dx.doi.org/10.18452/21383.
Texte intégralHuman brain is a complex dynamical system, whose complexity could be highly functional and characterize cognitive abilities or mental disorders. The APOE ɛ4 allele is a well-known genetic risk factor for the development of Alzheimer’s Disease and cognitive decline in later human life. The main goal of this study is to investigate the bridges between brain signal complexity, APOE genotype and cognitive performance among young adults under the framework of individual difference. After validating the reliability of Residue Iteration decomposition (RIDE), a method for analysis brain signals in the first study, I investigated in the second study how individual differences in APOE genotypes are associated with brain signal complexity measured with Multiscale Entropy (MSE) and cognitive ability. The second study demonstrated that APOE ε4 is associated with higher entropy at scale 1-4 and lower entropy at scale 5 and above, especially at frontal scalp regions and in an eyes open condition; in addition, there’s a stronger drop in MSE from closed to open eyes condition among ε4 carriers than non-carriers. The ε4 association with cognitive performance was complex, but basically ε4 seems to be associated with worse cognitive performance among lower educated people, whereas no such association appeared among the higher educated. Afterwards, the third study connected MSE with a different cognitive domain – face and object cognition abilities. We showed that 1) increased MSE for a closed eyes condition at all scales is associated with better cognitive performance. 2) Increased MSE at higher scales (7 or 8) was associated with tighter coupling between RIDE-extracted single trial stimulus evaluation speed at the neural level and reaction time at the behavior level. To summarize, the results of my doctoral study connected brain signal complexity, APOE genotype and cognitive behavior among young healthy adults, providing a deeper understanding of brain-behavior relationships and – potentially – for early AD diagnosis when cognitive decline is not yet evident.
Harris, Julian David. « Development of recombinant adeno-associated virus and second generation adenovirus vectors for the gene transfer of human apolipoprotein E (ApoE) in the APOE deficient mouse ». Thesis, Royal Holloway, University of London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.420867.
Texte intégralFilho, Sebastião Barreto de Brito. « Efeito da ingestão crônica de vinho sobre a homeostase glicêmica, lipídica e ponderal em camundongos ApoE Knockout ». Universidade do Estado do Rio de Janeiro, 2013. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=6770.
Texte intégralThe benefits to health related to regular consume of red wine includes different mechanisms in which are involved both ethanol and fenolics compounds of the wine. With the objective to evaluate glycemia, lipid profile and weight variations with regular use of red wine by ApoE Knockout mices, sixty adults ApoE Knockout mices weighing around 30g were distributed into 3 groups of 20 animals each: 1.Wine that received 50mL of wine plus 50mL of water, 2. Ethanol and Water groups, 6mL of ethanol plus 94mL of water and just water respectively for 4 months. We evaluate glycemia, weight variations and liver glycogen, triglycerides and cholesterol. The wine group had in relation to its mass body an area under the curve larger than the other two groups, but with a small percentage of increase. The concentration of liver triglycerides was higher in the wine 57% compared to ethanol group, which was 31.6% lower than the control (p<0.01%). The concentration of liver cholesterol was lower in wine (23.6%) and in ethanol group (24.5%) (p<0.05%). The liver glycogen concentration was higher in the wine (16%), although not reaching statistical significance. The fasting glicemia on the day of euthanasia was higher in the ethanol group compared to other groups, but not statistically significant difference. In histological analysis was not significantly different between groups, although the average weight in grams fat, retroperitoneal and subcutaneous was approximately two times higher in the wine group. It was concluded that in this study the regular and chronic use of red wine increased liver triglyceride, however alcohol decreases liver cholesterol. The increase of the triglyceride may be due to the high caloric value of wine or some lipogenic unknown property that led to an important increase in retroperitoneal and subcutaneous fat tissue in ApoE Knockout mice.
Wadas, Theresa M. « Relationships among APOE Genotypes, Inflammatory Markers, and Risk Factors among African Americans with Ischemic Stroke ». Diss., The University of Arizona, 2015. http://hdl.handle.net/10150/556235.
Texte intégralObregon, Tito Alexandra de. « APOE haplotypes in health, lessons from an Oklahoman African American population ». Oklahoma City : [s.n.], 2010.
Trouver le texte intégralNaumann, Sandy. « Gen-Umweltinteraktion bei alkoholabhängigen Patienten am Beispiel von ApoE und Homocystein ». kostenfrei, 2009. http://d-nb.info/999863649/34.
Texte intégralYoung, Elizabeth. « HDL-apoE content regulates the cell surface displacement of hepatic lipase ». Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28247.
Texte intégralJiang, Qingguang. « The role of ApoE and liver X receptors in Alzheimer's disease ». Cleveland, Ohio : Case Western Reserve University, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1212161307.
Texte intégralKarpe, Britta. « Effekt von Darbepoetin alfa auf die geschädigte Niere am ApoE(-/-)-Mausmodell ». kostenfrei, 2008. http://www.opus.ub.uni-erlangen.de/opus/volltexte/2008/1003/.
Texte intégralDumanis, Sonya Benjamina E. « Using APOE genotypes to identify new biomarkers for Alzheimer's disease risk ». Thesis, Georgetown University, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3559756.
Texte intégralAlzheimer's disease (AD), unlike the other leading causes of death, does not have a cure or an effective intervention strategy. The largest genetic risk factor for AD is APOE, with the ϵ4 allele increasing and the ϵ2 allele decreasing one's risk for the disease. It remains unclear how ApoE isoforms contribute to various AD-related pathological changes (e.g. amyloid plaques, synaptic and neuron loss). Here, we characterize the differences between the at risk group for AD (the ϵ4 carriers) and the not-at risk group (non-ϵ4 carriers), to determine what underlies APOE-related risk to AD.
To do this, we utilized APOE Targeted Replacement (TR) mice. These animals express the human APOE alleles (APOE-ϵ2, APOE-ϵ3, or APOE-ϵ4) under the mouse APOE promoter, and do not develop the plaques and tangles diagnostic of AD. We found that despite the lack of AD pathology, APOE-ϵ4 TR mice had alterations at the synapse. Specifically, APOE-ϵ4 TR mice have fewer dendritic spines at the post-synaptic terminal and simpler neuronal morphology compared to the other APOE genotypes. Pre-synaptically, we found that APOE-ϵ4 TR mice have reduced levels of glutaminase, increased levels of VGLUT1 and increased levels of glutamine (GLN). Taken together, these data suggest that the APOE-ϵ4 allele affects brain function well before AD pathogenesis occurs.
To begin addressing the mechanism by which APOE can impact dendritic spine morphology, we examined the role of the apoE receptor, ApoEr2. We found that increased surface levels of ApoEr2 promoted dendritic spine formation and that the ligand binding domain is necessary for us to observe these effects, suggesting that ApoEr2 may be involved in APOE related changes at the synapse.
To test whether there are CSF biomarkers of APOE-associated risk that could be followed in preventative therapeutic AD approaches, we examined levels of GLN in ante-mortem CSF samples from healthy controls. Consistent with our mouse studies, we found that APOE-ϵ4 carriers had higher levels of GLN compared to the other genotypes. These studies suggest that GLN may be a novel biomarker used to assess AD patients in their pre-clinical phases and as a therapeutic measure in preventative AD trials.
Mathias, Daniel. « Auswirkungen niedrig dosierter ionisierender Strahlung auf inflammatorische Marker des ApoE-/- -Mäuse-Herzens ». Doctoral thesis, Universitätsbibliothek Leipzig, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-221195.
Texte intégralLarramona, Arcas Raquel. « ApoE4 pathology in Alzheimer’s disease from the perspective of organelle dysfunction in astrocytes ». Doctoral thesis, Universitat Autònoma de Barcelona, 2018. http://hdl.handle.net/10803/666659.
Texte intégralAlzheimer’s disease is the most common form of dementia in advanced ages affecting more than 40 million people around the world. It is a complex disease that affects not only neurons but also astrocytes. Apolipoprotein E4 (ApoE4) has been described as the most important genetic risk factor for the sporadic form of the disease and interestingly, astrocytes are its main secretors. The research about its pathogenic mechanisms has mainly focused on its extracellular role. On the contrary, we analysed the dysregulations that endogenous intracellular ApoE4 causes on astrocytes. We focused on 2 principal physiological processes altered in Alzheimer’s disease: calcium signalling and mitochondrial functions. As cellular model, we used immortalized astrocytes that express human ApoE3 (non-associated with any pathology) or ApoE4. Using fluorescent calcium indicators and the technique of Calcium Imaging, we determined that ApoE4 astrocytes have altered calcium homeostasis as they have lower basal intracellular calcium levels but higher purinergic-induced calcium signals compared to ApoE3 astrocytes. A high V-ATPase activity, and hence, higher lysosomal calcium uptake in ApoE4 astrocytes explains these alterations. Moreover, lysosomal calcium release after purinergic receptor activation is followed by higher endoplasmic reticulum (ER) calcium mobilization in ApoE4 than in ApoE3 astrocytes. Extracellular calcium entry is similar in both cell types. Our studies also demonstrated that the lack of lipoproteins in the extracellular medium upregulates the magnitude of purinergic-elicited calcium responses in ApoE3 astrocytes, as extracellular calcium entry amplifies lysosomal calcium release. This feature is missing in ApoE4 astrocytes being the magnitude of calcium responses unaffected by extracellular lipoproteins. On the other hand, we described alterations in mitochondrial dynamics determined by real-time microscopy and fluorescent mitochondria labelling. In particular, ApoE4 cell mitochondria do not perform fission after inhibition of mitochondrial oxidative phosphorylation whereas ApoE3 astrocyte mitochondria perform it. In addition, ApoE4 astrocytes have increased mitochondrial motility, reduction of Parkin, a protein involved in mitophagy, and reduction in mitochondrial DNA content compared to ApoE3 astrocytes. In summary, we demonstrated, for the first time, that endogenous ApoE4 alters calcium signalling and mitochondrial functions in astrocytes. Taking into account that ApoE is expressed throughout the life of individuals, these astrocytic alterations might appear in the early stages of the Alzheimer’s disease. In order to advance in the detection of such early phases of the pathology, and since cerebrospinal fluid proteins reflect the cellular function of brain cells, we next identified a group of astrocytic proteins present in the cerebrospinal fluid related to Alzheimer’s disease that we propose as a functional astrocytic signature for early stages of the disease. This signature is composed of S100B, ApoE, prostaglandin D2 synthetase, cystatin 3, integral membrane protein 2C and clusterin. Overall, endogenous ApoE4 alters astrocyte functions, a phenomenon that can contribute to Alzheimer’s disease, but also, to its detection through cerebrospinal fluid biomarkers.
Dikotope, Sekgothe Abram. « Response of serum lipids to a fat meal in Black South African subjects with different apoe genotypes ». Thesis, University of Limpopo (Turfloop Campus), 2013. http://hdl.handle.net/10386/1059.
Texte intégralObjectives The present study investigated how the serum lipids responded to a high-fat meal in black South African subjects with different APOE genotypes, a population that until recently was reported to be consuming a traditional diet of low fat and high carbohydrates. Methods Sixty students (males and females) of the University of Limpopo, Turfloop Campus were successfully genotyped using Restriction Fragment Length Polymorphism (RFLP) and grouped into four APOE genotype groups; ε2, ε2/ε4, ε3 and ε4. Only thirty-three subjects volunteered to participate in the oral fat-tolerance test (OFTT), but two were excluded for having abnormal total cholesterol (6.05 mmol/l) and LDL cholesterol (3.12 mmol/l) so only 31 subjects were left. The numbers per group were ε2=5, ε2/ε4=8, ε3=9 and ε4=9. After an overnight fast blood was drawn for measurements of baseline serum parameters. Subjects were administered a high fat meal 30 minutes after the baseline blood sample was drawn. Blood was drawn at intervals of 20, 40, 60, 120, 180, 240, 300 and 360 minutes for measurements of postprandial serum parameter levels. Serum parameters measured were triglyceride, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, glucose and insulin. Results Mean levels of serum lipids at baseline in mmol/l were as follows; group 1[TG=0.69(0.55-0.81), TCHOL=3.10±0.29, HDL-C=1.12±0.32, LDLC= 1.67±0.28]; group 2 [TG=0.61(0.53-1.00), TCHOL=2.98±0.53, HDLC= 1.20±0.37, LDL-C=1.43±0.37]; group 3 [TG=0.67(0.28-0.86), TCHOL=2.96±0.54, HDL-C=1.22±0.30, LDL-C=1.46±0.47]; group 4 [TG=0.76(0.51-1.16), TCHOL=3.27±0.51, HDL-C=1.12±0.17, LDLC= 1.79±0.47]. There was no significant difference in the mean levels of baseline triglyceride, total cholesterol, low density lipoprotein cholesterol, and ix high density lipoprotein cholesterol between the APOE groups hence no significant difference in the response to a fatty meal. Conclusions There was no significant change in serum lipid concentrations after a fatty meal in individuals with different APOE genotypes in a population that consume a traditional diet of low fat and high carbohydrates. Due to the small sample size, the results should be interpreted with caution. A larger study is recommended to ascertain the role of APOE genotypes on serum lipid response to a fatty meal in Black South African population.
Filippini, Nicola. « Brain structure, function and connectivity associated with APOE genotype : what changes when ? » Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.525306.
Texte intégralFarsian, Farnas [Verfasser], et Jörg Heeren [Akademischer Betreuer]. « ApoE Regulates Corticospinal Neuronal Survival Through ApoER2 / Farnas Farsian. Betreuer : Jörg Heeren ». Hamburg : Staats- und Universitätsbibliothek Hamburg, 2013. http://d-nb.info/1045024538/34.
Texte intégralMcColl, Barry. « Pathophysiology of cerebral ischaemia : effects of APOE genotype on outcome and endocytosis ». Thesis, University of Glasgow, 2004. http://theses.gla.ac.uk/4324/.
Texte intégralGrace, Laurian Kerry. « The relationship between Alzheimer's disease, inflammation, the APOE genotype and neuronal integrity ». Doctoral thesis, University of Cape Town, 2013. http://hdl.handle.net/11427/3394.
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