Tau phosphorylation pathway genes and cerebrospinal fluid tau levels in Alzheimer's disease

Lynn M. Bekris, Steve Millard, Franziska Lutz, Gail Li, Doug R. Galasko, Martin R. Farlow, Joseph F. Quinn, Jeffrey A. Kaye, James B. Leverenz, Debby W. Tsuang, Chang En Yu, Elaine R. Peskind

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Alzheimer's disease (AD) is characterized by the presence in the brain of amyloid plaques, consisting predominately of the amyloid β peptide (Aβ), 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. Our hypothesis 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 5 kinase and 4 phosphatase genes, as well as 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. Rs7768046 in the FYN kinase gene and rs913275 in the PPP2R4 phosphatase gene were both associated with CSF p-tau and t-tau levels in AD. These SNPs were also differentially associated with either CSF t-tau (rs7768046) or CSF p-tau (rs913275) relative to t-tau levels in AD compared to controls. These results suggest that rs7768046 and rs913275 both influence CSF tau levels in an AD-associated manner.

Original languageEnglish (US)
Pages (from-to)874-883
Number of pages10
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume159 B
Issue number7
DOIs
StatePublished - Oct 2012

Keywords

  • AD
  • CSF
  • FYN
  • MAPT
  • PPP2R4

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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