Convergent genetic and expression data implicate immunity in Alzheimer's disease
Alzheimer's & Dementia , Volume 11 - Issue 6 p. 658- 671
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<sup>-12</sup> after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10<sup>-11</sup>), cholesterol transport (P = 2.96 × 10<sup>-9</sup>), and proteasome-ubiquitin activity (P = 1.34 × 10<sup>-6</sup>). 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.
|ALIGATOR, Alzheimer's disease, Cholesterol metabolism, Dementia, Endocytosis, Immune response, Neurodegeneration, Pathway analysis, Ubiquitination, Weighted gene co-expression network analysis|
|Alzheimer's & Dementia|
|Organisation||Department of Clinical Genetics|
Jones, L, Lambert, J.-C, Wang, L, Choi, S.-H, Harold, D, Vedernikov, A, … MRC CFAS, . (2015). Convergent genetic and expression data implicate immunity in Alzheimer's disease. Alzheimer's & Dementia, 11(6), 658–671. doi:10.1016/j.jalz.2014.05.1757