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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Michael H Malek-Ahmadi1,2,3, Savar Sharma4, Fawaz Stipho5

  • 1Banner Alzheimer's Institute, Phoenix, AZ, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary

Plasma phosphorylated tau-217 (ptau-217) assays show excellent accuracy in identifying preclinical Alzheimer's disease (AD) in cognitively unimpaired individuals. The large effect size of ptau-217 differences supports its use as a diagnostic tool for preclinical AD.

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Area of Science:

  • Biomarkers of neurodegenerative diseases
  • Alzheimer's disease diagnostics
  • Clinical proteomics

Background:

  • Plasma phosphorylated tau-217 (ptau-217) shows strong correlation with in-vivo Alzheimer's disease (AD) pathology.
  • The ability of ptau-217 assays to differentiate cognitively unimpaired (CU) individuals with and without AD pathology requires further evaluation.

Purpose of the Study:

  • To evaluate mean differences in ptau-217 levels between amyloid-positive and amyloid-negative CU older adults.
  • To assess the diagnostic accuracy of ptau-217 for identifying preclinical AD in CU individuals.

Main Methods:

  • Systematic literature search of PubMed, Embase, and Ebsco databases up to August 1, 2024.
  • Meta-analysis of 14 studies (5,763 participants) for mean differences using Hedge's g.
  • Meta-analysis of 9 studies (3,626 participants) for diagnostic accuracy using pooled area under the curve (AUC).

Main Results:

  • A large effect size (Hedge's g = 1.45) was observed for ptau-217 mean differences between amyloid-positive and amyloid-negative CU individuals, with high heterogeneity.
  • The pooled AUC was 0.84, indicating excellent diagnostic accuracy of ptau-217 for identifying amyloid-positive CU individuals.
  • Subgroup analyses by assay platform, amyloid detection method, and study setting did not significantly alter the main findings.

Conclusions:

  • Plasma ptau-217 assays demonstrate high accuracy in identifying individuals in the preclinical stage of AD.
  • The significant mean differences in ptau-217 levels further validate its utility as a diagnostic biomarker for preclinical AD.