No association between the alpha 2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression

Citation
K. Blennow et al., No association between the alpha 2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression, J NEURAL TR, 107(8-9), 2000, pp. 1065-1079
Citations number
46
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEURAL TRANSMISSION
ISSN journal
03009564 → ACNP
Volume
107
Issue
8-9
Year of publication
2000
Pages
1065 - 1079
Database
ISI
SICI code
0300-9564(2000)107:8-9<1065:NABTA2>2.0.ZU;2-P
Abstract
A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the alpha 2-macroglobulin (A2M) gene (A2M-2) has been suggested to be as sociated 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 patien ts with AD (n = 449) and age-matched controls (n = 349). Neuropathologicall y confirmed diagnoses were available in 199 cases (94 AD and 107 control ca ses). We found no increase in A2M-2 genotype or allele frequencies in AD (2 7.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked in crease (p < 0.0001) in ApoE epsilon 4 genotype or allele frequencies was fo und in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), su ggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE epsilon 4 allele. No change in A2M exon 17-1 8mRNA 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 flui d 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 A2 M-2 allele and AD in the present study, and the lack of abnormalities in th e A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.