P4‐118: Tau phosphorylation pathway genes and cerebrospinal fluid tau levels in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is characterized by the presence in the brain of amyloid plaque, consisting primarily of A β, and neurofibrillary tangles, consisting primarily of tau. Hyper-phosphorylated-tau (p-tau) contributes to neuronal damage, and both p-tau and total-tau (t-tau) levels are elevated in AD cerebrospinal fluid (CSF) compared to cognitively normal controls. The hypothesis of this investigation was that increased ratios of CSF phosphorylated-tau levels relative to total-tau levels correlate with regulatory region genetic variation of kinase or phosphatase genes biologically associated with the phosphorylation status of tau. Eighteen SNPs located within 5' and 3' regions of kinase and phosphatase genes and two SNPs within regulatory regions of the MAPT gene were chosen for this analysis. The study sample consisted of 101 AD patients and 169 cognitively normal controls. The rs7768046 and rs913275 SNPs were both associated with CSF p-tau and t-tau levels in AD. The rs7768043 SNP and rs913275 were also differentially associated with either CSF t-tau or CSF p-tau relative to t-tau levels in AD compared to controls, respectively. These results suggest that the rs7668046 of the FYN kinase gene and the rs913275 of the PPP2R4 phosphatase gene influence CSF tau levels in an AD specific manner.