An integrated systems‐level analysis of the molecular changes resulting from systemic inflammation in Alzheimer's disease. (1st February 2022)

• Record Type: Journal Article
• Authors: MacBean, Lachlan F; Smith, Rebecca G.; Smith, Adam R.; Nicoll, James AR; Boche, Delphine; Lunnon, Katie
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 3
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-01
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.051373
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: In the current study we have performed an Epigenome‐Wide Association Study (EWAS) comparing bulk brain tissue in individuals with AD and non‐demented controls with or without a systemic infection, followed by targeted validation in isolated microglia. Method: DNA methylation is being quantified from 300 post‐mortem brain samples, 75 AD cases with infection, 75 AD cases without an infection, 75 non‐demented controls with infection and 75 non‐demented controls without an infection. DNA methylation of isolated microglia is also being quantified and gene expression data collected from the same samples to allow integration of epigenetic and transcriptomic data. Result: Statistical analyses performed using our established EWAS pipeline will identify significant differentially methylated positions. This is particularly expected to be observable in regions across genes implicated in disease pathology. Conclusion: Through cross‐examination of the four study groups we will identify novel patterns of methylation in those suffering from neuroinflammation not previously observed, also providing critical insight into the underlying molecular changes that arise in microglia as a result of neuroinflammation.