There was no significant difference in the severity of CAA between individuals with the A2M deletion allele and those without in the AD, non-AD, or total cases.
Our findings do not support the fact that the previously reported positive association between A2M deletion polymorphism and AD modifies the disease risk in the studied population.Am.J. Med.Genet.(Neuropsychiatr.Genet.)96:775-777, 2000.
Our results failed to demonstrate an association between this polymorphism and Japanese sporadic AD, and the A2MI1000V mutation does not seem to be a risk factor per se for sporadic AD.
In the brain of Alzheimer's disease (AD) patients, alpha(2)M has been localized to diffuse amyloid plaques. alpha(2)M also binds soluble beta-amyloid, of which it mediates degradation.
Recent reports have suggested that genetic polymorphisms in the alpha-2 macroglobulin (A2M) gene are associated with an increased risk for Alzheimer's disease.
To evaluate the genetic factors for AD among a Chinese population in Taiwan, we studied the polymorphisms of six candidate genes of Alzheimer's disease (AD), including the regulatory region of apolipoprotein E (Apo-E, G-186T), the promoter of apolipoprotein E (Apo-E, A-491T), the bleomycin hydrolase gene (BH, A1450G), a mutation of alpha(2)-macroglobulin gene (A2M G2998A), low-density lipoprotein receptor-related protein gene (LRP, C766T), and alpha(1)-antichymotrypsin gene (ACT, -15Ala/Thr) in AD patients and non-affected elder individuals among Taiwanese Chinese.
Apolipoprotein E (apoE), the lipoprotein receptor related protein (LRP) and alpha-2 macroglobulin (alpha2M) have been proposed as a functional complex involved in amyloid clearance, a crucial event for Alzheimer's disease development.
We conclude that the BBB removes Ass from the brain largely via age-dependent, LRP-1-mediated transport that is influenced by alpha(2)M and/or apoE, and may be impaired in AD.
In conclusion, our data suggests that the A2M D allele is a modest risk factor for late-onset sporadic AD in Koreans, and the AD risk conferred by the A2M D allele increases in APOE epsilon4 negative subjects.
Our data suggest that attenuation of IL-1beta-induced alpha(2)M synthesis/release by blocking NF-kappaB activation may potentially be 'protective' against the development of late-onset AD.
Therefore, we conclude that in our samples, the A2M I/V genotype might be a susceptibility variant, even with minor effect, for both sporadic AD and PD.
In this study, we examined the subunit and conformational structure of alpha(2)M in AD plasma samples, and its capacity to bind trypsin, transforming growth factor-beta1, and Abeta.
Substantial linkage disequilibrium was detected across the gene as a whole, and haplotype analysis also showed significant association between AD and groups of A2M polymorphisms.