Alpha-2 macroglobulin gene in early- and late-onset Alzheimer disease

Alpha-2-macroglobulin (A2M) is a proteinase inhibitor that is present in se nile plaques and may play a role in metabolism of amyloid beta (A beta) pep tide. Recently it was reported that inheritance of the deletion allele (A2M -2) confers increased risk for late-onset Alzheimer disease (AD) with signi ficance of this effect similar to the is an element of 4 allele of apolipop rotein E (APOE). We examined the distribution of A2M genotypes and alleles in a cohort of 146 AD patients and 160 age-matched non-demented individuals . There was no evidence for association in the total sample or in subsets s tratified by age or APOE is an element of 4 status. These results suggest t hat this polymorph ism is not a strong genetic risk factor for either early -or late-onset forms of the disorder. However, they do not exclude the poss ibility that an AD susceptibility allele is located elsewhere in A2M or a n earby gene. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.