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alpha(2)-Macroglobulin polymorphisms in Alzheimer's disease and dementia with Lewy bodies

Lookup NU author(s): Professor Ian McKeith, Dr Clive Ballard, Emeritus Professor Robert Perry, Professor Jim Edwardson, Dr Christopher Morris


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Dementia with Lewy bodies (DLB) is the second most common cause of dementia in the elderly after Alzheimer's disease (AD). The apolipoprotein E gene (APOE) is a major risk factor, but can only account for similar to 50% of AD cases. Whole genome scanning in late-onset AD families has suggested that a locus on chromosome 12 may contribute significantly to disease development. Recently the alpha(2)-macroglobulin gene (A2M) on chromosome 12 has been suggested as a candidate locus for AD. We therefore determined the influence of two polymorphisms in A2M, a pentanucleotide deletion 5' to the bait domain exon, and a valine to isoleucine polymorphism in the thiolester site of the protein, in AD and DLB cohorts. No evidence was observed for an association between the thiolester or deletion polymorphisms and AD or DLB alone or when accounting for the APOE epsilon 4 allele. We did, however, identify a non-significant excess of deletion homozygotes in the AD and DLB groups. This genotype accounted for 4% of disease cases but was absent in the control population. Given that the A2M deletion polymorphism is non-functional, the chromosome 12 AD/DLB locus may be situated elsewhere and not with these A2M polymorphisms. NeuroReport 10:1507-1510 (C) 1999 Lippincott Williams & Wilkins.

Publication metadata

Author(s): McKeith IG; Edwardson JA; Perry RH; Morris CM; Ballard CA; Singleton AB; Gibson AM; Ince PG

Publication type: Article

Publication status: Published

Journal: Neuroreport

Year: 1999

Volume: 10

Issue: 7

Pages: 1507-1510

Print publication date: 14/05/1999

ISSN (print): 0959-4965

ISSN (electronic): 1473-558X

Publisher: Lippincott Williams & Wilkins