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Chromosome 21 BACE2 haplotype associates with Alzheimer's disease: A two-stage study

Lookup NU author(s): Dr Tuomo Polvikoski


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Genetic linkage studies have provided evidence for a late-onset Alzheimer's disease (AD) susceptibility locus on chromosome 21q. We have tested, in a two-stage association study, whether allelic or haplotype variation of the beta-amyloid cleaving enzyme-2 (BACE2) locus on chromosome 21q affects the risk of late-onset AD. In stage-1, an unselected population-based sample of Finns aged 85 years or over (n = 515) was analysed. Neuropathologic examination including beta-amyloid load quantification was possible in over 50% (n = 264) of these subjects. AD patients (n = 100) and controls (n = 48) were defined by modified neuropathological NIA-RI criteria. Positive associations were taken as a hypothesis, and tested in stage-2 using 483 AD families from the USA. Four single nucleotide polymorphisms (SNPs) of BACE2 gene were tested in stage-1. A SNP close to exon-6 was associated with neuropathologically verified AD (p = 0.02) and also with beta-amyloid load in non-selected autopsied subjects after conditioning with APOE genotype (p = 0.001). In haplotype analysis a specific, relatively common haplotype (H5) was found to associate with AD (p = 0.004) and a second haplotype (H7) showed a weaker association with protection against AD (p = 0.04). In stage-2, the SNP association was not replicated, whereas the haplotype H5 association was replicated (p = 0.004) and a trend to association was found with the putative protective haplotype H7 (two-sided p = 0.08). BACE2 haplotype association with AD in two independent datasets provides further evidence for an AD susceptibility locus on chromosome 21q within or close to BACE2. © 2005 Elsevier B.V. All rights reserved.

Publication metadata

Author(s): Myllykangas L, Wavrant-De Vrieze F, Polvikoski T, Notkola I-L, Sulkava R, Niinisto L, Edland SD, Arepalli S, Adighibe O, Compton D, Hardy J, Haltia M, Tienari PJ

Publication type: Article

Publication status: Published

Journal: Journal of the Neurological Sciences

Year: 2005

Volume: 236

Issue: 1-2

Pages: 17-24

Print publication date: 15/09/2005

ISSN (print): 0022-510X

ISSN (electronic): 1878-5883

Publisher: Elsevier


DOI: 10.1016/j.jns.2005.04.008

PubMed id: 16023140


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