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Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease

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 thes...

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Hauptverfasser: Jones, Lesley (VerfasserIn) , Bussche, Hendrik van den (VerfasserIn) , Frölich, Lutz (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: November 15, 2010
In: PLOS ONE
Year: 2010, Jahrgang: 5, Heft: 11, Pages: 1-11
ISSN:1932-6203
DOI:10.1371/journal.pone.0013950
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1371/journal.pone.0013950
Verlag, kostenfrei, Volltext: http://www.plosone.org/article/info:doi/10.1371/journal.pone.0013950
Volltext
Verfasserangaben:Lesley Jones, Hendrik van den Bussche, Lutz Frölich [und 79 weitere]
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 14.09.2023
Beschreibung:Online Resource
ISSN:1932-6203
DOI:10.1371/journal.pone.0013950

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