title: Convergent genetic and expression data implicate immunity in Alzheimer's disease.
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.
mesh_terms: D000465:Algorithms; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide
keywords: ALIGATOR; Alzheimer's disease; Cholesterol metabolism; Dementia; Endocytosis; Immune response; Neurodegeneration; Pathway analysis; Ubiquitination; Weighted gene co-expression network analysis