rs1467967

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.

This case-control association study in 4,124 Spanish Alzheimer's disease cases and 3,290 controls demonstrates that the MAPT H1 haplotype, tagged by rs1800547, is a risk factor for AD (OR=1.12, p=0.0025) primarily in APOE ε4 non-carriers (OR=1.15, p=0.0022). Pooled analysis of two Spanish datasets totaling 17,996 individuals shows strongest AD risk in the oldest APOE ε4 non-carriers, suggesting MAPT H1 variants may track a genuine risk allele through a tau-dependent pathway less dependent on amyloid burden.