Depletion of potential A2M risk haplotype for Alzheimer's disease in long-lived individuals.

Authors:
Friederike Flachsbart, Amke Caliebe, Michael Nothnagel, Rabea Kleindorp, Susanna Nikolaus, Stefan Schreiber, Almut Nebel
Year of publication:
2010
Volume:
18
Issue:
1
Issn:
1018-4813
Journal title abbreviated:
EUR J HUM GENET
Journal title long:
European journal of human genetics
Impact factor:
4.580
Abstract: 
Risk alleles for age-related diseases are expected to decrease in frequency in the population strata of increasing age. Consistent with this hypothesis, earlier studies showed a depletion of the Alzheimer''s disease risk factor APOE*epsilon4 in long-lived individuals (LLIs). To evaluate whether this observation also holds for a previously suggested Alzheimer''s disease risk haplotype in the A2M gene, we analyzed this particular haplotype in 1042 German LLIs (aged 95-100 years) and 1040 younger individuals (aged 60-75 years). Our results show a significant depletion of this haplotype in LLIs, thus confirming it as a mortality factor in the elderly. Consequently, our data support an involvement of the suggested A2M risk haplotype in the pathogenesis of Alzheimer''s disease and adds new evidence to the risk-allele depletion hypothesis.