Diagnostic accuracy of phosphorylated tau217 in detecting Alzheimer's disease pathology among cognitively impaired and unimpaired: A systematic review and meta-analysis

Abstract

Our review summarizes the diagnostic accuracy of plasma and cerebrospinal fluid (CSF) phosphorylated tau 217 (p-tau217) in detecting amyloid and tau pathology on positron emission tomography (PET). We systematically reviewed studies that reported the diagnostic accuracy of plasma and CSF p-tau217, searching MEDLINE/PubMed, Scopus, and Web of Science through August 2024. The accuracy of p-tau217 in predicting amyloid and tau pathology on PET was evaluated in 30 studies. Both plasma and CSF p-tau217 effectively detect amyloid and tau PET deposition. Plasma p-tau217 showed 82% sensitivity for detecting amyloid and 83% for tau, with 86% and 83% specificity, respectively. CSF p-tau217 had 79% sensitivity for amyloid and 91% for tau, with 91% and 84% specificity. p-tau217 effectively identifies Alzheimer's disease (AD) pathology. Plasma p-tau217 was comparable to CSF p-tau217 in detecting amyloid deposition on PET. Despite being less sensitive for detecting tau deposition on PET, plasma p-tau217 can be an efficient screening tool for underlying AD pathology. HIGHLIGHTS: Plasma phosphorylated tau 217 (p-tau217) serves as a viable biomarker alternative to cerebrospinal fluid p-tau217 due to the strong concordance between their results. Plasma p-tau217 accurately identifies amyloid and tau positron emission tomography (PET) positivity, exhibiting a low rate of false negatives and positives, thereby establishing it as a reliable diagnostic tool for Alzheimer's disease (AD). Plasma p-tau217 demonstrates slightly higher accuracy in predicting amyloid PET positivity compared to tau PET positivity. Plasma p-tau217 demonstrates higher predictive accuracy in detecting AD pathology among cognitively impaired individuals, compared to cognitively unimpaired individuals, suggesting its enhanced utility as a diagnostic biomarker in clinical settings.

Keywords: Alzheimer's disease; amyloid beta positron emission tomography imaging; cerebrospinal fluid biomarkers; diagnostic test accuracy; phosphorylated tau 217; plasma biomarkers; positron emission tomography; tau positron emission tomography imaging.

FIGURE 1

PRISMA flowchart. PET, positron emission tomography; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta‐analysis; p‐tau, phosphorylated tau.

FIGURE 2

p‐tau217 has been proposed to be the most accurate fluid biomarker of AD pathology among various ethnic, racial, and clinical groups. The map illustrates the geographical distribution of included studies, highlighting the countries of origin of the cohorts included in this meta‐analysis and the number of individuals reported in the included studies, which were from the United States (MCSA, WRAP, UCSF Memory and Aging Center, Pittsburgh ADRC, Mayo Clinic ADRC, Florida ADRC),, , , , , , , , , Canada (Triad),, , , Sweden (Biofinder),, , , , , , , Switzerland (Memory Center), Belgium (F‐PACK), Spain (ALFA),, China (community‐based longitudinal cohort), Thailand (Memory Clinic), Japan (J‐TRC), and Australia (AIBL, ADNeT)., AD, Alzheimer's disease; ADNeT, Australian Dementia Network; ADRC, Alzheimer's Disease Research Center; AIBL, Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing; ALFA, Alzheimer's and Families; F‐PACK, Flemish Prevent Alzheimer's Disease Cohort KU Leuven; MCSA, Mayo Clinic Study on Aging; p‐tau217, phosphorylated tau 217; UCSF, University of California San Francisco, WRAP, Wisconsin Registry for Alzheimer's Prevention.

FIGURE 3

The SROC curve evaluates the performance of p‐tau217 in predicting PET positivity. The curve plots sensitivity against the false positive rate, summarizing the diagnostic accuracy across multiple studies. The curve includes a 95% confidence region to illustrate the uncertainty in the summary estimates. Each dot represents a study's individual sensitivity and false positive rate, with the SROC curve capturing the overall performance trend. A, SROC curve for plasma p‐tau217 in predicting amyloid PET positivity, with an AUC of 0.91 and sensitivity of 0.82 (95% CI: 0.79–0.84). B, SROC curve for plasma p‐tau217 in predicting tau PET positivity, with an AUC of 0.90 and sensitivity of 0.83 (95% CI: 0.78–0.87). C, SROC curve for CSF p‐tau217 in predicting amyloid PET positivity, with an AUC of 0.88 and sensitivity of 0.79 (95% CI: 0.73–0.84). D, SROC curve for CSF p‐tau217 in predicting tau PET positivity, with an AUC of 0.95 and sensitivity of 0.91 (sensitivity 95% CI: 0.87–0.95). AUC, area under the curve; CI, confidence interval; CSF, cerebrospinal fluid; PET, positron emission tomography; p‐tau217, phosphorylated tau 217; SROC, summary receiver operating characteristic.