Alpha2-macroglobulin polymorphism is not associated with AD or AD-type neuropathology in the Japanese
1Department of Neurology, Tokyo Medical and Dental University, Japan.
Background:
alpha2-Macroglobulin (A2M) forms the complex with amyloid beta-protein (Abeta) and is associated with degradation of Abeta. It has been reported that the A2M gene (A2M) exon 18 splice acceptor deletion polymorphism influences the development of AD, regardless of apolipoprotein E-epsilon4 (APOE-epsilon4) status.
Objective:
To determine the effect of A2M polymorphism on the development of AD and AD-type neuropathologic changes.
Methods:
The authors examined the A2M and APOE genotypes, the densities of the senile plaques (SPs), SPs with dystrophic neurites (NPs), and neurofibrillary tangles (NFTs) in the brains of 62 postmortem-confirmed sporadic AD and 90 nondemented patients from an autopsy series of elderly Japanese subjects.
Results:
There was no association of the A2M polymorphism with AD, age at onset, or duration of illness in AD. The A2M polymorphism was not associated with the SPs, NPs, or NFTs in AD or nondemented patients. The results remained insignificant, even when the A2M genotype groups were divided into subgroups by APOE-epsilon4 status.
Conclusion:
The A2M polymorphism does not affect the development of sporadic AD or formation of AD-type neuropathologic changes.
Insights
The alpha2-Macroglobulin (A2M) polymorphism does not influence Alzheimer's disease (AD) development or neuropathologic changes like amyloid plaques and neurofibrillary tangles. This finding holds true regardless of apolipoprotein E-epsilon4 (APOE-epsilon4) status.
Area of Science:
- Neuroscience
- Genetics
- Pathology
Background:
- Alpha2-Macroglobulin (A2M) plays a role in amyloid beta-protein (Abeta) degradation.
- Previous studies suggested a link between A2M exon 18 polymorphism and Alzheimer's Disease (AD) development, independent of APOE-epsilon4 status.
Purpose of the Study:
- To investigate the impact of A2M gene polymorphism on the incidence of sporadic AD.
- To determine the association between A2M polymorphism and AD-related neuropathologic hallmarks.
Main Methods:
- Genotyping for A2M and APOE.
- Quantification of senile plaques (SPs), neuritic plaques (NPs), and neurofibrillary tangles (NFTs) in postmortem brain tissue.
- Analysis of 62 sporadic AD and 90 non-demented Japanese subjects.
Main Results:
- No significant association was found between A2M polymorphism and AD development, age of onset, or disease duration.
- A2M polymorphism did not correlate with the density of SPs, NPs, or NFTs in either AD or non-demented individuals.
- Subgroup analysis by APOE-epsilon4 status did not alter the observed lack of association.
Conclusions:
- The A2M exon 18 splice acceptor deletion polymorphism does not appear to influence the development of sporadic Alzheimer's Disease.
- This A2M polymorphism is not associated with the formation of key neuropathologic changes characteristic of AD.
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