کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5624260 | 1406242 | 2015 | 14 صفحه PDF | دانلود رایگان |
BackgroundLate-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.MethodsThe ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.ResultsALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (PÂ =Â 3.27Â ÃÂ 10â12 after multiple testing correction for pathways), regulation of endocytosis (PÂ =Â 1.31Â ÃÂ 10â11), cholesterol transport (PÂ =Â 2.96Â ÃÂ 10â9), and proteasome-ubiquitin activity (PÂ =Â 1.34Â ÃÂ 10â6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05).ConclusionsThe immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
Journal: Alzheimer's & Dementia - Volume 11, Issue 6, June 2015, Pages 658-671