ALPHA -2 MACROGLOBULIN POLYMORPHISM AND ALZHEIMER DISEASE RISK IN THE UK

There is a genetic component in the aetiology of Alzheimer disease1 (AD). Recently, Blacker et al. reported an odds ratio of 3.56 for being affected by AD in individuals carrying at least one copy of an -2 macroglobulin gene (A2M) allele (A2M*2) corresponding to a deletion near the 5´ splice site of exon 18 (2). Cases were aged 50 years and older and 22% had autopsy diagnoses2. This effect was independent of APOE. We tried to replicate these findings using three different samples. Our first sample was composed of 125 autopsy-confirmed AD cases from Brain Banks in England and 218 elderly non-demented controls. Where age of onset was documented, 3 cases were younger than 50 years and 30 cases were 50-65 years. In cases where the age at onset was not available, 35 individuals died before age 66, including 2 before 50 years. We used non-demented elderly English individuals as controls: 59 from Ely (a town 14 miles from Cambridge) aged 70 years and older meeting neither DSM-III-R nor AGECAT dementia criteria3; and 159 from Cambridge aged 84 years and older with Mini Mental State Examination (MMSE) scores of more than 23 (3). Our second sample was composed of 53 pairs of age-matched (within 5 years) demented cases and controls, aged 70 years and older, from the epidemiologically based Ely component of the Medical Research Council Cognitive Function and Ageing Study4. Cases met both DSM-III-R and AGECAT criteria3 and controls met neither of these dementia criteria. The controls used in our first sample included those from the matched case-control series with six unmatched controls from the same cohort.