Association between an α2 macroglobulin DNA polymorphism and late-onset Alzheimer's disease

An association between a five-base-pair deletion/ insertion DNA polymorphism at the (alpha(2) macroglobulin gene (A2M) and late-onset Alzheimer's disease (LOAD) has been recently described. We developed a PCR assay to analyze this polymorphism in 190 LOAD patients (older than 65 years) and 400 controls from Spain, Controls were stratified into three groups: <65 years (n = 200), 65 to 80 years (n = 100), and 81 years or older (n = 100), We found a significantly higher frequency of carriers of the D allele in patients older than 81 years compared to controls older than 81 years (p = 0.0012), In addition, the frequency of the D allele was significantly lower in controls older than 81 years compared to controls younger than 65 (p = 0.048), Our work suggests that the D allele confers an age-dependent increased risk to develop late-onset Alzheimer's disease. (C) 1999 Academic Press.