title: Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease.
Creators: name: Jones, Lesley
name: Holmans, Peter A.
name: Hamshere, Marian L.
name: Harold, Denise
name: Moskvina, Valentina
name: Ivanov, Dobril
name: Pocklington, Andrew
name: Abraham, Richard
name: Hollingworth, Paul
name: Sims, Rebecca
name: Gerrish, Amy
name: Pahwa, Jaspreet Singh
name: Jones, Nicola
name: Stretton, Alexandra
name: Morgan, Angharad R.
name: Lovestone, Simon
name: Powell, John
name: Proitsi, Petroula
name: Lupton, Michelle K.
name: Brayne, Carol
name: Rubinsztein, David C.
name: Gill, Michael
name: Lawlor, Brian
name: Lynch, Aoibhinn
name: Morgan, Kevin
name: Brown, Kristelle S.
name: Passmore, Peter A.
name: Craig, David
name: McGuinness, Bernadette
name: Todd, Stephen
name: Holmes, Clive
name: Mann, David
name: Smith, A. David
name: Love, Seth
name: Kehoe, Patrick G.
name: Mead, Simon
name: Fox, Nick
name: Rossor, Martin
name: Collinge, John
name: Maier, Wolfgang
name: Jessen, Frank
name: Schürmann, Britta
name: Heun, Reinhard
name: Kölsch, Heike
name: van den Bussche, Hendrik
name: Heuser, Isabella
name: Peters, Oliver
name: Kornhuber, Johannes
name: Wiltfang, Jens
name: Dichgans, Martin
name: Frölich, Lutz
name: Hampel, Harald
name: Hüll, Michael
name: Rujescu, Dan
name: Goate, Alison M.
name: Kauwe, John S. K.
name: Cruchaga, Carlos
name: Nowotny, Petra
name: Morris, John C.
name: Mayo, Kevin
name: Livingston, Gill
name: Bass, Nicholas J.
name: Gurling, Hugh
name: McQuillin, Andrew
name: Gwilliam, Rhian
name: Deloukas, Panos
name: Al-Chalabi, Ammar
name: Shaw, Christopher E
name: Singleton, Andrew B
name: Guerreiro, Rita
name: Mühleisen, Thomas W.
name: Nöthen, Markus M.
name: Moebus, Susanne
name: Jöckel, Karl-Heinz
name: Klopp, Norman
name: Wichmann, Heinz-Erich
name: Rüther, Eckhard
name: Carrasquillo, Minerva M.
name: Pankratz, V. Shane
name: Younkin, Steven G.
name: Hardy, John
name: O'Donovan, Michael C.
name: Owen, Michael J.
name: Williams, Julie
Publisher: name: Universitätsbibliothek der Ludwig-Maximilians-Universität München
Year: 2010
Subjects: subject: 610

description: 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. 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. 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. 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.