rs913275

This candidate gene association study examined 18 SNPs in tau phosphorylation pathway genes (kinases and phosphatases) in relation to cerebrospinal fluid (CSF) tau levels in 101 Alzheimer's disease (AD) patients and 169 cognitively normal controls. Two SNPs significantly correlated with CSF tau levels after multiple comparison correction: rs7768046 in the FYN kinase gene (associated with increased CSF t-tau in AD, P=0.0007 Holm-corrected) and rs913275 in the PPP2R4 phosphatase gene (associated with increased CSF p-tau and t-tau in AD, P=0.0024 Holm-corrected). These findings suggest that genetic variation in genes regulating tau phosphorylation influences CSF tau levels in an AD-associated manner.

A review of genetic discoveries in Alzheimer's disease using cerebrospinal fluid (CSF) levels of amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau181) as endophenotypes. The paper discusses multiple GWAS and sequencing studies that identified novel AD risk variants including rs9877502 (3q28, p=4.89×10⁻⁹), rs514716 in GLIS3 (p=1.07×10⁻⁸), and rs6922617 in TREM cluster (p=3.58×10⁻⁸), as well as functional characterization of known AD variants including APOE, MAPT, and TREM2. The review emphasizes the increased statistical power of using quantitative CSF biomarkers compared to traditional case-control designs.