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- W2079863513 abstract "Quantitative traits such as CSF tau levels offer more power than case-control tests in identifying genes implicated in Alzheimer's disease (AD). In our previous studies we found several SNPs, located in the genes encoding the regulatory subunit of the protein phosphatase 2B (PPP3R1), and the microtubule-associated protein tau (MAPT) gene, that are associated with CSF tau levels. In this study we tested the impact of these SNPs on risk for AD, age at onset and rate of disease progression Allelic and genotypic association with risk for AD was tested using a Fisher's exact test. Association with age at onset was carried out using Kaplan-Meier curves and a log-rank test. We used a mixed linear model to determine whether there are differences in the rate of progression as a function of genotype. Progression of disease was measured by annual change in CDR sum of boxes (CDR-SB). We found no association between rs1868402 and risk for AD or age at onset. However, individuals homozygous for the rs1868402 allele associated with higher CSF tau levels showed a six fold faster change in CDR-SB than individuals of other genotypes (p = 0.0026). We found significant epistasis between rs1868402 (PPP3R1) and rs3785883 (MAPT) (P = 4.00×10-04). In contrast we found that the ∊4 allele of APOE, which is strongly associated with CSF AB42 levels, is not associated with progression rate in these samples. Our analyses suggest that genetic variants associated with CSF Aβ42 levels also influence risk and age at onset (as in the case of APOE) but variants associated with CSF tau and ptau181 levels may have a greater impact on rate of progression. Variants that influence disease progression may have significant clinical benefit. For example, these variants have the potential to predict more accurately the time from diagnosis to functional impairment that may require nursing home placement. Stratification of samples by such SNPs will enable cheaper and more efficient clinical trials by selecting individuals expected to have faster rates of progression." @default.
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- W2079863513 date "2010-07-01" @default.
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- W2079863513 title "P1-064: SNPs associated with CSF tau levels modify rate of progression in Alzheimer's disease" @default.
- W2079863513 doi "https://doi.org/10.1016/j.jalz.2010.05.612" @default.
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