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DOI 10.1371/journal.pone.0013950

Медицинская библиотека · PloS one · 2010

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

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

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод пока не подготовлен

Аннотация

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.

Для цитирования: Jones Lesley, Holmans Peter A, Hamshere Marian L, Harold Denise, Moskvina Valentina, Ivanov Dobril, Pocklington Andrew, Abraham Richard, Hollingworth Paul, Sims Rebecca, Gerrish Amy, Pahwa Jaspreet Singh, Jones Nicola, Stretton Alexandra, Morgan Angharad R, Lovestone Simon, Powell John, Proitsi Petroula, Lupton Michelle K, Brayne Carol, Rubinsztein David C, Gill Michael, Lawlor Brian, Lynch Aoibhinn, Morgan Kevin, Brown Kristelle S, Passmore Peter A, Craig David, McGuinness Bernadette, Todd Stephen, Holmes Clive, Mann David, Smith A David, Love Seth, Kehoe Patrick G, Mead Simon, Fox Nick, Rossor Martin, Collinge John, Maier Wolfgang, Jessen Frank, Schürmann Britta, Heun Reinhard, Kölsch Heike, van den Bussche Hendrik, Heuser Isabella, Peters Oliver, Kornhuber Johannes, Wiltfang Jens, Dichgans Martin, Frölich Lutz, Hampel Harald, Hüll Michael, Rujescu Dan, Goate Alison M, Kauwe John S K, Cruchaga Carlos, Nowotny Petra, Morris John C, Mayo Kevin, Livingston Gill, Bass Nicholas J, Gurling Hugh, McQuillin Andrew, Gwilliam Rhian, Deloukas Panos, Al-Chalabi Ammar, Shaw Christopher E, Singleton Andrew B, Guerreiro Rita, Mühleisen Thomas W, Nöthen Markus M, Moebus Susanne, Jöckel Karl-Heinz, Klopp Norman, Wichmann H-Erich, Rüther Eckhard, Carrasquillo Minerva M, Pankratz V Shane, Younkin Steven G, Hardy John, O'Donovan Michael C, Owen Michael J, Williams Julie. Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease.. PloS one. 2010. DOI: 10.1371/journal.pone.0013950.

Предметные рубрики MeSH

Alzheimer DiseaseApolipoproteins ECholesterolChromosome MappingGenetic Predisposition to DiseaseGenome, HumanGenome-Wide Association StudyHumansImmune SystemPolymorphism, Single Nucleotide
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