A genome-wide association study of plasma phosphorylated tau181

Neurobiol Aging. 2021 Oct;106:304.e1-304.e3. doi: 10.1016/j.neurobiolaging.2021.04.018. Epub 2021 May 4.


Plasma phosphorylated tau at threonine-181 (P-tau181) demonstrates promise as an accessible blood-based biomarker specific to Alzheimer's Disease (AD), with levels recently demonstrating high predictive accuracy for AD-relevant pathology. The genetic underpinnings of P-tau181 levels, however, remain elusive. This study presents the first genome-wide association study of plasma P-tau181 in a total sample of 1153 participants from 2 independent cohorts. No loci, other than those within the APOE genomic region (lead variant = rs429358, beta = 0.32, p =8.44 × 10-25) demonstrated association with P-tau181 at genome-wide significance (p < 5 × 10-08), though rs60872856 on chromosome 2 came close (beta = -0.28, p = 3.23 × 10-07, nearest gene=CYTIP). As the APOE ε4 allele is already a well-established genetic variant associated with AD, this study found no evidence of novel genetic associations relevant to plasma P-tau181, though presents rs60872856 on chromosome 2 as a candidate locus to be further evaluated in future larger size GWAS.

Keywords: Genome wide association study; P-tau181; Plasma biomarkers; Plasma phosphorylated tau181.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / genetics*
  • Biomarkers / blood
  • Chromosomes, Human, Pair 2 / genetics
  • Cohort Studies
  • Female
  • Genome-Wide Association Study / methods*
  • Humans
  • Male
  • Negative Results
  • Phosphorylation
  • tau Proteins / blood*


  • Biomarkers
  • tau Proteins