@article {7018, title = {Convergent genetic and expression data implicate immunity in Alzheimer{\textquoteright}s disease.}, journal = {Alzheimers Dement}, volume = {11}, year = {2015}, month = {2015 Jun}, pages = {658-71}, abstract = {

BACKGROUND: Late-onset Alzheimer{\textquoteright}s disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer{\textquoteright}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 {\texttimes} 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 {\texttimes} 10(-11)), cholesterol transport (P = 2.96 {\texttimes} 10(-9)), and proteasome-ubiquitin activity (P = 1.34 {\texttimes} 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.

}, keywords = {Algorithms, Alzheimer Disease, Brain, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide}, issn = {1552-5279}, doi = {10.1016/j.jalz.2014.05.1757} }