Title
Convergent genetic and expression data implicate immunity in Alzheimer's disease Convergent genetic and expression data implicate immunity in Alzheimer's disease
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
,
Subject
Human medicine
Source (journal)
Alzheimer's & dementia. - Place of publication unknown
Volume/pages
11(2015) :6 , p. 658-671
ISSN
1552-5260
ISI
000357231900008
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Background Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10−12 after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10−11), cholesterol transport (P = 2.96 × 10−9), and proteasome-ubiquitin activity (P = 1.34 × 10−6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
E-info
https://repository.uantwerpen.be/docman/iruaauth/c364e5/5fc84b8948f.pdf
Full text (open access)
https://repository.uantwerpen.be/docman/irua/698be8/9534.pdf
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