The relative expression level of BACE1 gene in the stem cell treatment group was lower than that in the AD control group (P<0.05), but that of A2M gene was increased (P<0.05).
We recently reported that alpha-2 macroglobulin (A2M) is a biomarker of neuronal injury in Alzheimer's disease (AD) and identified a network of nine genes co-expressed with A2M in the brain.
Collectively these novel findings suggest that A2M is associated with preclinical AD, reflects early neuronal injury in the disease course and may be responsive to tau phosphorylation in the brain through the RCAN1-calcineurin pathway.
Drug response from pharmacogenetic viewpoint after 3-year follow-up of AD patients and Clinical Dementia Rating (CDR) analysis demonstrated that AD patients carrying bigenic genotype IL-6 CC-A2M AG (ΔCDR = 4.5) and male patients with IL-6 CC genotype (ΔCDR = 3.83) provided the best response and the A2M GG genotype (ΔCDR = 7.97) and bigenic genotype IL-6 GG-A2M GG (ΔCDR = 8.5) conferred the worst response to the rivastigmine, suggesting likely involvement of genotype-specific response to rivastigmine therapy in AD patients.
The TREM2 variant is associated with: (i) AD (odds ratio: 4.76; P = .014); (ii) increased density of amyloid plaques and neurofibrillary tangles in multiple brain regions; (iii) increased TREM2 (P = .041) and TYROBP (P = .006) gene expression; (iv) decreased TREM2 protein levels (P = .016); and (v) upregulation of proinflammatory cytokines (regulated on activation, normal T cell expressed and secreted [RANTES] and interferon [IFN] gamma) (P = .003) and nominal downregulation of protective markers (α2-macroglobulin, interleukin 4 or IL-4, and ApoA1) (P = .018).
The meta-analysis suggests that there is no enough evidence for associations of A2M gene polymorphisms (5 bp I/D, Ile1000Val) with AD risk at present, even after stratification by ethnicity and APOE ε4 with genotypes of polymorphism sites.
The coexistence of at least one allele Val (A2M-Val+) and one allele C (LRP1-C+) increased up two times the risk of AD (OR 2.32; 95% CI 1.23-4.35; p<0.009).
Two other genes with mixed support as genetic risk factors for AD, A2M (alpha-2-macroglobulin) and LRP (low-density lipoprotein receptor-related protein), have not been studied in relation to memory among nondemented adults.
Through combination-analysis of the data about the A2M-I/D and the A2M-Ile1000Val variants, the A2M gene was suggested to be associated with Alzheimer's disease.
Low-density lipoprotein receptor-related protein 1 (LRP1) and alpha-2-macroglobulin (A2M) are two plausible candidate genes for Alzheimer disease (AD) based on their important biological function and positional information.
These results indicated that A2M-D allele was probably a weak AD protective factor, and there was a possible interaction of APOE-epsilon 4 and A2M-G alleles to increase AD risk in Mainland Han Chinese.
Earlier identified regions on chromosomes 10 and 12, nor the effect of the alpha-2-macroglobulin (A2M) I/D polymorphism on Alzheimer's disease could be confirmed in our study.
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.
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 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 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.