Plasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer's disease

Alzheimers Dement. 2024 Aug;20(8):5617-5628. doi: 10.1002/alz.14073. Epub 2024 Jun 28.

Abstract

Background: This study investigated the potential of phosphorylated plasma Tau217 ratio (pTau217R) and plasma amyloid beta (Aβ) 42/Aβ40 in predicting brain amyloid levels measured by positron emission tomography (PET) Centiloid (CL) for Alzheimer's disease (AD) staging and screening.

Methods: Quantification of plasma pTau217R and Aβ42/Aβ40 employed immunoprecipitation-mass spectrometry. CL prediction models were developed on a cohort of 904 cognitively unimpaired, preclinical and early AD subjects and validated on two independent cohorts.

Results: Models integrating pTau217R outperformed Aβ42/Aβ40 alone, predicting amyloid levels up to 89.1 CL. High area under the receiver operating characteristic curve (AUROC) values (89.3% to 94.7%) were observed across a broad CL range (15 to 90). Utilizing pTau217R-based models for low amyloid levels reduced PET scans by 70.5% to 78.6%.

Discussion: pTau217R effectively predicts brain amyloid levels, surpassing cerebrospinal fluid Aβ42/Aβ40's range. Combining it with plasma Aβ42/Aβ40 enhances sensitivity for low amyloid detection, reducing unnecessary PET scans and expanding clinical utility.

Gov identifiers: NCT02956486 (MissionAD1), NCT03036280 (MissionAD2), NCT04468659 (AHEAD3-45), NCT03887455 (ClarityAD) HIGHLIGHTS: Phosphorylated plasma Tau217 ratio (pTau217R) effectively predicts amyloid-PET Centiloid (CL) across a broad spectrum. Integrating pTau217R with Aβ42/Aβ40 extends the CL prediction upper limit to 89.1 CL. Combined model predicts amyloid status with high accuracy, especially in cognitively unimpaired individuals. This model identifies subjects above or below various CL thresholds with high accuracy. pTau217R-based models significantly reduce PET scans by up to 78.6% for screening out individuals with no/low amyloid.

Keywords: blood‐based biomarkers; diagnosis; disease continuum; disease staging; patient monitoring; patient screening; prediction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / diagnostic imaging
  • Amyloid beta-Peptides* / blood
  • Biomarkers / blood
  • Brain* / diagnostic imaging
  • Brain* / metabolism
  • Clinical Trials as Topic
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / blood
  • Peptide Fragments / cerebrospinal fluid
  • Phosphorylation
  • Positron-Emission Tomography*
  • tau Proteins* / blood
  • tau Proteins* / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • amyloid beta-protein (1-40)
  • Biomarkers
  • Peptide Fragments
  • tau Proteins

Associated data

  • ClinicalTrials.gov/NCT02956486
  • ClinicalTrials.gov/NCT04468659
  • ClinicalTrials.gov/NCT03036280
  • ClinicalTrials.gov/NCT03887455

Grants and funding