Age at onset: an essential variable for the definition of genetic risk factors for sporadic Alzheimer's disease.

Abstract:

:The aim of our work was to detect minor loci acting as Alzheimer's disease (AD) genetic markers. We divided 206 AD patients and 186 individuals as controls into six age at onset/age-dependent groups. We studied polymorphisms of the genes of apolipoprotein E (APOE) and its promoter, cathepsin D, butyrylcholinesterase, cystatin C, methionine synthase, and cystathionine beta-synthase. Our results demonstrated that data analysis according to age at onset allows the detection of minor genetic risk factors for AD. Thus, the Th1/E47cs-G allele was an independent AD risk factor after 80 years, whereas the catD-T, BChE-K, CBS-844ins68, and CBS-VNTR 19 alleles are independent AD risk factors after 75 years. On the other hand, the CST3-A allele was an independent AD risk factor before 60 years while the CBS-VNTR allele 21 was an independent AD risk factor before 64 years. In contrast, the MS-AA genotype was an AD risk factor unrelated to age at onset. In conclusion, two main tasks remain to be accomplished to facilitate early detection of people at risk of developing AD: (1) the establishment of common criteria to carry out association studies for different genetic markers, including the introduction of AD age at onset as a crucial variable in each study, and (2) the definition of global and population-specific genetic markers for each age at onset AD subgroup.

journal_name

Ann N Y Acad Sci

authors

Beyer K,Lao JI,Latorre P,Ariza A

doi

10.1196/annals.1322.021

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

260-78

eissn

0077-8923

issn

1749-6632

pii

1057/1/260

journal_volume

1057

pub_type

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