Convergent genetic and expression data implicate immunity in Alzheimer's disease

International Genomics of Alzheimer's Disease Consortium (IGAP), Patrick Kehoe

Research output: Contribution to journalArticle (Academic Journal)peer-review

116 Citations (Scopus)

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.

Original languageEnglish
JournalAlzheimer's and Dementia
DOIs
Publication statusPublished - 20 Dec 2014

Bibliographical note

Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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