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Convergent genetic and expression data implicate immunity in Alzheimer's disease
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2015 (English)In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 6, 658-671 p.Article in journal (Refereed) Published
Abstract [en]

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 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.

Place, publisher, year, edition, pages
2015. Vol. 11, no 6, 658-671 p.
Keyword [en]
Alzheimer's disease, Dementia, Neurodegeneration, Immune response, Endocytosis, Cholesterol metabolism, Ubiquitination, Pathway analysis, ALIGATOR, Weighted gene co-expression network analysis
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URN: urn:nbn:se:uu:diva-260145DOI: 10.1016/j.jalz.2014.05.1757ISI: 000357231900008OAI: oai:DiVA.org:uu-260145DiVA: diva2:846723
Available from: 2015-08-18 Created: 2015-08-17 Last updated: 2015-08-18Bibliographically approved

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Lannfelt, LarsIngelsson, Martin
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