Α-2 macroglobulin gene and alzheimer disease

Access through your institution Buy or subscribe Blacker _et al_.1 reported an association between a deletion in exon 18 of the α-2 macroglobulin (_A2M_) gene and Alzheimer disease (AD) in a

sample of affected and unaffected siblings from families segregating AD. They observed that the degree of conferred risk for AD in _A2M_ allele 2 (_A2M*2_) carriers was similar in magnitude

to that for carriers of the apolipoprotein (_APOE_) _ɛ4_ allele (_APOE*E4_). We set out to test for a similar association in a powerful, case-control sample composed of 2,616 individuals

taken from populations from Europe and the United States. In addition, we extended our analysis of the National Institute of Mental Health (NIMH) family samples studied by Blacker _et al_.1

using linkage and association approaches. We pooled this NIMH series (270 sibpairs) with a similar series of 125 sibpairs collected through the auspices of the National Institution of Aging

(NIA) at the Indiana Alzheimer cell repository to increase the power of our analysis. We studied four independent association samples of unrelated AD patients with onset over 50 years and

relevant controls (Table 1) and diagnosed AD patients according to NINCDS-ADRDA (ref. 2) criteria with either probable or definite AD. We calculated that this sample had over 99% power to

detect an effect of equivalent size to that reported by Blacker _et al_.1 in their familial sample (odds ratio (OR)=3.56), assuming a stringent α level of 0.001. Furthermore, we calculated

that our sample was sufficiently powerful (80%) to detect an extremely small effect (OR≥1.2) assuming an α level of 0.05. This is a preview of subscription content, access via your

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* Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Blacker, D. et al. _Nature Genet._ 19, 357–360 (1998). Article  CAS  Google Scholar  *

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_Hum. Mol. Genet._ 8, 237–245 (1999). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank the clinicians and staff of the Mayo Institute and Washington University

School of Medicine, NIMH and NIA. This work was supported by the Medical Research Council (UK), the Institut National pour la Santé Et la Recherche Médicale (INSERM), the Institut Pasteur de

Lille, the Conseil Régional du Nord-Pas de Calais axe régional de recherche sur les maladies neurodégénératives et le vieillissement cérébral and the Fondation pour la Recherche Médicale,

The Mayo Foundation, National Institute of Health, the Alzheimer's Disease Association and the Nettie and Rebecca Brown Foundation. AUTHOR INFORMATION Author notes * Varuni

Rudrasingham, Fabienne Wavrant-De Vrièze, Jean-Charles Lambert and Sumi Chakraverty: These authors contributed equally to this work AUTHORS AND AFFILIATIONS * Department of Psycological

Medicine, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN Varuni Rudrasingham, Patrick Kehoe, Frances Rice, Stephanie Carty, Peter Holmans, Michael J. Owen & Julie

Williams * Birdsallh Building, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, 32084, Florida, USA Fabienne Wavrant-De Vrièze, Richard Crook, Jordi Pérez-Tur & John Hardy *

CJF 95-05 INSERM, Institut Pasteur de Lille, 1 Rue du Pr Calmette, Lille, 59019, Cedex, France Jean-Charles Lambert, Philippe Amouyel, Bernard Frigard, Dominique Cottel & 

Marie-Christine Chartier-Harlin * Departments of Neurology, Psychiatry and Genetics, Washington University School of Medicine, 4940 Children's Place, St. Louis, 63110, Missouri, USA

Sumi Chakraverty, William Wu, John C. Morris, Peter Holmans & Alison Goate * Department of Neurology, Mayo Clinic Rochester, Rochester, 55905, Minnesota, USA Ronald Petersen * Section of

Old Age Psychiatry, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK Nigel Tunstall & Simon Lovestone Authors * Varuni Rudrasingham View author publications You can also

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permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Rudrasingham, V., Wavrant-De Vrièze, F., Lambert, JC. _et al._ α-2 macroglobulin gene and Alzheimer disease. _Nat Genet_ 22, 17–19 (1999).

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