ABCA2 is a strong genetic risk factor for early-onset Alzheimer's disease
Recent epidemiological, biological and genetic data indicate a relationship between cholesterol and Alzheimer's disease (AD) including the association of polymorphisms of ABCA1 (a gene that is known to participate in cholesterol and phospholipid transport) with AD prevalence. Based on these dat...
Main Authors: | , , , , , , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2005-02-01
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Series: | Neurobiology of Disease |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996104002207 |
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doaj-c8e0e03b225243b1b5dda3f8c2d79066 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sandrine Macé Emmanuelle Cousin Sylvain Ricard Emmanuelle Génin Emmanuel Spanakis Carole Lafargue-Soubigou Bérengère Génin Raphaël Fournel Sandrine Roche Gilles Haussy Florence Massey Stéphane Soubigou Georges Bréfort Patrick Benoit Alexis Brice Dominique Campion Melvyn Hollis Laurent Pradier Jésus Benavides Jean-François Deleuze |
spellingShingle |
Sandrine Macé Emmanuelle Cousin Sylvain Ricard Emmanuelle Génin Emmanuel Spanakis Carole Lafargue-Soubigou Bérengère Génin Raphaël Fournel Sandrine Roche Gilles Haussy Florence Massey Stéphane Soubigou Georges Bréfort Patrick Benoit Alexis Brice Dominique Campion Melvyn Hollis Laurent Pradier Jésus Benavides Jean-François Deleuze ABCA2 is a strong genetic risk factor for early-onset Alzheimer's disease Neurobiology of Disease Association study Alzheimer's disease ABCA2 Cholesterol |
author_facet |
Sandrine Macé Emmanuelle Cousin Sylvain Ricard Emmanuelle Génin Emmanuel Spanakis Carole Lafargue-Soubigou Bérengère Génin Raphaël Fournel Sandrine Roche Gilles Haussy Florence Massey Stéphane Soubigou Georges Bréfort Patrick Benoit Alexis Brice Dominique Campion Melvyn Hollis Laurent Pradier Jésus Benavides Jean-François Deleuze |
author_sort |
Sandrine Macé |
title |
ABCA2 is a strong genetic risk factor for early-onset Alzheimer's disease |
title_short |
ABCA2 is a strong genetic risk factor for early-onset Alzheimer's disease |
title_full |
ABCA2 is a strong genetic risk factor for early-onset Alzheimer's disease |
title_fullStr |
ABCA2 is a strong genetic risk factor for early-onset Alzheimer's disease |
title_full_unstemmed |
ABCA2 is a strong genetic risk factor for early-onset Alzheimer's disease |
title_sort |
abca2 is a strong genetic risk factor for early-onset alzheimer's disease |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2005-02-01 |
description |
Recent epidemiological, biological and genetic data indicate a relationship between cholesterol and Alzheimer's disease (AD) including the association of polymorphisms of ABCA1 (a gene that is known to participate in cholesterol and phospholipid transport) with AD prevalence. Based on these data, we postulated that genetic variation in the related and brain-specific ABCA2 gene leads to increase risk of AD. A large case–control study was conducted where the sample was randomly divided into a hypothesis-testing sample (230 cases/286 controls) and a validation sample (210 cases/233 controls). Among the 45 SNPs we tested, one synonymous SNP (rs908832) was found significantly associated with AD in both samples. Additional analyses performed on the whole sample showed a very strong association between this marker and early-onset AD (OR = 3.82, 95% C.I. = [2.00 – 7.30], P = 5 × 10−5). Further research is needed to understand the functional role of this polymorphism. However, together with the reported associations of AD with APOE, CYP46A1 and ABCA1, the present result adds a very significant support for the role of cholesterol and phospholipid homeostasis in AD and a rationale for testing novel cholesterol homeostasis-related therapeutic strategies in AD. |
topic |
Association study Alzheimer's disease ABCA2 Cholesterol |
url |
http://www.sciencedirect.com/science/article/pii/S0969996104002207 |
work_keys_str_mv |
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doaj-c8e0e03b225243b1b5dda3f8c2d790662021-03-20T04:50:18ZengElsevierNeurobiology of Disease1095-953X2005-02-01181119125ABCA2 is a strong genetic risk factor for early-onset Alzheimer's diseaseSandrine Macé0Emmanuelle Cousin1Sylvain Ricard2Emmanuelle Génin3Emmanuel Spanakis4Carole Lafargue-Soubigou5Bérengère Génin6Raphaël Fournel7Sandrine Roche8Gilles Haussy9Florence Massey10Stéphane Soubigou11Georges Bréfort12Patrick Benoit13Alexis Brice14Dominique Campion15Melvyn Hollis16Laurent Pradier17Jésus Benavides18Jean-François Deleuze19Aventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceINSERM U 535, Hôpital Paul Brousse, 94817 Villejuif, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceINSERM U289, Boulevard de l'Hôpital, 75013 Paris, FranceINSERM EMI 9906, Faculté de Médecine, IFRMP, 76000 Rouen, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, FranceAventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry-sur-Seine, France; Corresponding author. Evry Genetics Center, Aventis Pharma, 2 rue Gaston Crémieux, CP5705, 91057 Evry, France. Fax: +33 1 60 79 87 10.Recent epidemiological, biological and genetic data indicate a relationship between cholesterol and Alzheimer's disease (AD) including the association of polymorphisms of ABCA1 (a gene that is known to participate in cholesterol and phospholipid transport) with AD prevalence. Based on these data, we postulated that genetic variation in the related and brain-specific ABCA2 gene leads to increase risk of AD. A large case–control study was conducted where the sample was randomly divided into a hypothesis-testing sample (230 cases/286 controls) and a validation sample (210 cases/233 controls). Among the 45 SNPs we tested, one synonymous SNP (rs908832) was found significantly associated with AD in both samples. Additional analyses performed on the whole sample showed a very strong association between this marker and early-onset AD (OR = 3.82, 95% C.I. = [2.00 – 7.30], P = 5 × 10−5). Further research is needed to understand the functional role of this polymorphism. However, together with the reported associations of AD with APOE, CYP46A1 and ABCA1, the present result adds a very significant support for the role of cholesterol and phospholipid homeostasis in AD and a rationale for testing novel cholesterol homeostasis-related therapeutic strategies in AD.http://www.sciencedirect.com/science/article/pii/S0969996104002207Association studyAlzheimer's diseaseABCA2Cholesterol |