Diagnostic value of plasma phosphorylated tau181 in Alzheimer's disease and frontotemporal lobar degeneration

Nat Med. 2020 Mar;26(3):387-397. doi: 10.1038/s41591-020-0762-2. Epub 2020 Mar 2.

Abstract

With the potential development of new disease-modifying Alzheimer's disease (AD) therapies, simple, widely available screening tests are needed to identify which individuals, who are experiencing symptoms of cognitive or behavioral decline, should be further evaluated for initiation of treatment. A blood-based test for AD would be a less invasive and less expensive screening tool than the currently approved cerebrospinal fluid or amyloid β positron emission tomography (PET) diagnostic tests. We examined whether plasma tau phosphorylated at residue 181 (pTau181) could differentiate between clinically diagnosed or autopsy-confirmed AD and frontotemporal lobar degeneration. Plasma pTau181 concentrations were increased by 3.5-fold in AD compared to controls and differentiated AD from both clinically diagnosed (receiver operating characteristic area under the curve of 0.894) and autopsy-confirmed frontotemporal lobar degeneration (area under the curve of 0.878). Plasma pTau181 identified individuals who were amyloid β-PET-positive regardless of clinical diagnosis and correlated with cortical tau protein deposition measured by 18F-flortaucipir PET. Plasma pTau181 may be useful to screen for tau pathology associated with AD.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis*
  • Amyloid / metabolism
  • Amyloid beta-Peptides / blood
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Cognition
  • Female
  • Frontotemporal Lobar Degeneration / blood*
  • Frontotemporal Lobar Degeneration / diagnosis*
  • Frontotemporal Lobar Degeneration / genetics
  • Frontotemporal Lobar Degeneration / pathology
  • Gray Matter / diagnostic imaging
  • Gray Matter / pathology
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neurofilament Proteins / blood
  • Phosphorylation
  • Positron-Emission Tomography
  • Severity of Illness Index
  • tau Proteins / blood*
  • tau Proteins / cerebrospinal fluid
  • tau Proteins / genetics

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Biomarkers
  • Neurofilament Proteins
  • neurofilament protein L
  • tau Proteins