No association between the a2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression
2000 (English)In: Journal of neural transmission, ISSN 0300-9564, Vol. 107, no 8-9, 1065-1079 p.Article in journal (Refereed) Published
A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the a2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE e4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE e4 allele. No change in A2M exon 17-18mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.
Place, publisher, year, edition, pages
2000. Vol. 107, no 8-9, 1065-1079 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-27884DOI: 10.1007/s007020070052Local ID: 12644OAI: oai:DiVA.org:liu-27884DiVA: diva2:248436