Genetic association of alpha(2)-macroglobulin with Alzheimer's disease in a Finnish elderly population

Recently, two studies have reported an association between the alpha(2)-mac roglobulin gene on chromosome 12 and late-onset Alzheimer's disease, wherea s others have not been able to replicate these findings. By using a prospec tive population-based study, we have investigated the relation between two polymorphisms in this gene with the presence of the disease and also with t he extent of pathological changes in the cerebral cortex. The Vantaa 85+ St udy includes all 601 persons, at least 85 years of age, who were living in Vantaa, Finland, on April 1, 1991. The neocortical beta -amyloid protein lo ad and the number of neurofibrillary tangles were determined on tissue sect ions by using methenamine silver staining and a modified Bielschowsky stain ing, respectively. The A/A genotype in exon 24 of the alpha(2)-macroglobuli n gene was associated with neuropathologically defined diagnosis of Alzheim er's disease according to the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) criteria and with an increase in the neocortical beta -amyloid protein load. The effect of this association was stronger in the a polipoprotein E epsilon 4-negative group. Therefore, genetic variability in the alpha(2)-macroglobulin gene is a risk factor associated with neuropath ologically defined Alzheimer's disease in our population, as well as with t he extent of neocortical P-amyloid protein deposition.