Journal
PLOS ONE
Volume 5, Issue 11, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0013950
Keywords
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Categories
Funding
- Wellcome Trust
- Medical Research Council (MRC, UK)
- Alzheimer's Research Trust (ART)
- Welsh Assembly Government
- Alzheimer's Society
- Ulster Garden Villages
- Northern Ireland Research and Development Office
- Royal College of Physicians-Dunhill Medical Trust
- Trinity College group
- Bristol Research into Alzheimer's and Care of the Elderly
- Oxford Project to Investigate Memory and Ageing (OPTIMA) group
- Motor Neurone Disease Association
- MRC
- US National Institutes of Health (NIH)
- Barnes Jewish Foundation
- Charles and Joanne Knight Alzheimer's Research Initiative
- NIH
- Robert and Clarice Smith and Abigail Van Buren AD Research Program
- UCL Hospital/UCL Biomedical Centre
- Helmholtz Zentrum Munchen
- German Research Center for Environmental Health
- BMBF
- German National Genome Research Network
- Munich Center of Health Sciences
- National Institute on Aging (NIA)
- NIA, NIH, Department of Health and Human Services [Z01 AG000950-06]
- University of Antwerp
- Fund for Scientific Research-Flanders
- Belgian Federal Science Policy Office [P6/43]
- Alzheimers Research UK [ART-NCG2008A-1, ART-RF2007-3, ART-BIG2009-1, ART-PG2010-1] Funding Source: researchfish
- Medical Research Council [MC_U123192748, G0600974, MC_U123160651, G0601846, G0701075, G0801418, G0300429, G0801418B, G0900688] Funding Source: researchfish
- MRC [G0600974, G0701075, G0300429, G0801418, MC_U123160651, MC_U123192748, G0900688, G0601846] Funding Source: UKRI
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Background: Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes. Methodology: We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset. Principal Findings: We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD. Significance: Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches.
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