© 2015, Elsevier Inc. All rights reserved.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.

Original publication




Journal article


Alzheimer's and Dementia

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658 - 671