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Understanding the mechanisms and pathways of Alzheimer’s disease in APOE genotype sub-populations

Alzheimer’s disease (AD) is a neurodegenerative disease classified pathologically by the presence of tau tangles and amyloid plaques. The largest genetic risk factor for AD is the APOE ε4 allele, while the APOE ε2 allele has been linked to a protective effect for AD. Recent studies demonstrated that APOE genotypes are linked to unique omics signatures and pathological features relating to AD, such as blood-brain barrier breakage. To investigate the role of APOE genotype in AD, I analyzed different levels of omic data in blood and brain. I analyzed transcriptomic data derived from autopsied brains using network and differential gene expression approaches to identify genes and pathways involved in the APOE ε2 protective mechanism for AD. Additionally, I identified APOE genotype-specific pathways and networks involved in both blood and brain function in AD using blood and brain tissue gene expression from mostly the same individuals. Lastly, I analyzed the association of methylation of DNA from blood and brain samples with AD to identify APOE and AD specific methylation signatures and potential drug targets. Collectively, this thesis emphasizes the utility of investigating APOE genotypes individually to identify novel pathways and potential drug targets within AD subpopulations.

Identiferoai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/47474
Date07 November 2023
CreatorsPanitch, Rebecca
ContributorsFarrer, Lindsay A., Jun, Gyungah R.
Source SetsBoston University
Languageen_US
Detected LanguageEnglish
TypeThesis/Dissertation

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