Plasma P-tau181 in Alzheimer's disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer's dementia

Nat Med. 2020 Mar;26(3):379-386. doi: 10.1038/s41591-020-0755-1. Epub 2020 Mar 2.


Plasma phosphorylated tau181 (P-tau181) might be increased in Alzheimer's disease (AD), but its usefulness for differential diagnosis and prognosis is unclear. We studied plasma P-tau181 in three cohorts, with a total of 589 individuals, including cognitively unimpaired participants and patients with mild cognitive impairment (MCI), AD dementia and non-AD neurodegenerative diseases. Plasma P-tau181 was increased in preclinical AD and further increased at the MCI and dementia stages. It correlated with CSF P-tau181 and predicted positive Tau positron emission tomography (PET) scans (area under the curve (AUC) = 0.87-0.91 for different brain regions). Plasma P-tau181 differentiated AD dementia from non-AD neurodegenerative diseases with an accuracy similar to that of Tau PET and CSF P-tau181 (AUC = 0.94-0.98), and detected AD neuropathology in an autopsy-confirmed cohort. High plasma P-tau181 was associated with subsequent development of AD dementia in cognitively unimpaired and MCI subjects. In conclusion, plasma P-tau181 is a noninvasive diagnostic and prognostic biomarker of AD, which may be useful in clinical practice and trials.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism
  • Biomarkers / blood
  • Dementia / blood*
  • Diagnosis, Differential
  • Disease Progression*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neuropathology
  • Phosphorylation
  • Proportional Hazards Models
  • ROC Curve
  • tau Proteins / blood*


  • Amyloid beta-Peptides
  • Biomarkers
  • tau Proteins