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Alpha-2 macroglobulin gene in early- and late-onset Alzheimer disease
G I Korovaitseva1, S Premkumar, A Grigorenko
1Mental Health Research Center, Russian Academy of Medical Sciences, Moscow.
Abstract:
Alpha-2-macroglobulin (A2M) is a proteinase inhibitor that is present in senile plaques and may play a role in metabolism of amyloid beta (A beta) peptide. Recently it was reported that inheritance of the deletion allele (A2M-2) confers increased risk for late-onset Alzheimer disease (AD) with significance of this effect similar to the epsilon4 allele of apolipoprotein 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 stratified by age or APOE epsilon4 status. These results suggest that this polymorphism is not a strong genetic risk factor for either early- or late-onset forms of the disorder. However, they do not exclude the possibility that an AD susceptibility allele is located elsewhere in A2M or a nearby gene.
Insights
The Alpha-2-macroglobulin (A2M) deletion allele (A2M-2) does not appear to be a significant genetic risk factor for Alzheimer disease (AD). This study found no association between A2M genotypes and AD risk in the examined cohort.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Alpha-2-macroglobulin (A2M) is a proteinase inhibitor found in senile plaques, potentially involved in amyloid beta (A beta) peptide metabolism.
- The A2M deletion allele (A2M-2) was recently suggested as a risk factor for late-onset Alzheimer disease (AD), comparable to APOE epsilon4.
Purpose of the Study:
- To investigate the association between A2M genotypes and Alzheimer disease (AD) risk.
- To determine if the A2M-2 allele is a significant genetic risk factor for AD.
Main Methods:
- Genotyping of A2M alleles in a cohort of 146 AD patients and 160 age-matched controls.
- Analysis of A2M genotype and allele distribution across the total sample and stratified subgroups (age, APOE epsilon4 status).
Main Results:
- No statistically significant evidence of association between A2M genotypes/alleles and AD was found in the overall sample.
- Stratified analyses by age and APOE epsilon4 status also revealed no significant association.
Conclusions:
- The A2M polymorphism, specifically the A2M-2 allele, does not appear to be a strong genetic risk factor for early- or late-onset Alzheimer disease.
- The study does not rule out the possibility of AD susceptibility alleles within A2M or nearby genes.