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- W2980579119 abstract "Alzheimer's disease (AD) polygenic burden, in the form of the polygenic hazard score (PHS), was recently linked to increased cortical levels of Aβ and increased decline in cognitive function (Tan et al., 2019, https://doi.org/10.1093/brain/awy327). We compared PHS to conventional polygenic risk scores (PRS), computed using the latest AD GWAS (Kunkle et al., 2019, https://doi.org/10.1038/s41588-019-0358-2), and their associations to cerebrospinal fluid (CSF) biomarkers Aβ, Tau and phosphorylated Tau, cortical amyloid burden and cognitive decline. We used data from 995 white subjects in the AD Neuroimaging Initiative (ADNI) database with available genome-wide genotyping data and who did not contribute to the ADGC GWAS. PRS were computed using PRSice with a p-value cutoff of 1e-05. PHS were obtained directly from ADNI. Linear models stratified by diagnosis were used to test the association of PHS and PRS with baseline values of Aβ, Tau and p-Tau in 807 subjects and regional amyloid burden in 822 subjects. Linear mixed effects (LME) models were used to assess the effect of PHS and PRS on decline in CDR-SB, memory and executive function in 601 non-demented subjects providing 4465 observations. PHS and PRS exhibited high correlation (r2=0.74). Both CSF Tau and p-Tau were associated with polygenic burden, while CSF Aβ was not (Table 1). The association between polygenic burden and cortical amyloid was only moderate (Figure 1). Only PRS was associated with decline in CDR-SB, but no other cognitive measures (Table 2)." @default.
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- W2980579119 date "2019-07-01" @default.
- W2980579119 modified "2023-09-28" @default.
- W2980579119 title "P4-490: ALZHEIMER'S DISEASE POLYGENIC BURDEN BEYOND APOE ACTS STRONGER ON TAU THAN ON AMYLOID" @default.
- W2980579119 doi "https://doi.org/10.1016/j.jalz.2019.08.036" @default.
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