Depletion of potential A2M risk haplotype for Alzheimer's disease in long-lived individuals.
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.
Flachsbart
Friederike
F
Institute of Clinical Molecular Biology, Christian-Albrechts University and University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
Caliebe
Amke
A
Nothnagel
Michael
M
Kleindorp
Rabea
R
Nikolaus
Susanna
S
Schreiber
Stefan
S
Nebel
Almut
A
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008136:Longevity / Q000235:genetics*; D000511:alpha-Macroglobulins / Q000235:genetics*
D001057:Apolipoproteins E; D000511:alpha-Macroglobulins