Age-dependent diagnostic and correlational architecture of multiplex plasma biomarkers in Alzheimer's disease: a cross-ethnic, cross-platform validation study.
Plasma p-tau217 diagnoses Alzheimer's disease more accurately in early-onset than late-onset patients.
Age-dependent diagnostic and correlational architecture of multiplex plasma biomarkers in Alzheimer's disease: a cross-ethnic, cross-platform validation study.
Plasma phosphorylated tau-217 (p-tau217) is one of the most accurate blood-based biomarkers for Alzheimer's disease (AD), yet whether its diagnostic and correlational properties vary with age at onset has not been systematically examined.
We measured eight plasma biomarkers (tau, amyloid, neurodegeneration, neuroinflammation) via automated chemiluminescence immunoassay in a Chinese memory clinic cohort (n = 604; amyloid positron emission tomography (positron emission tomography) reference), with validation in the Alzheimer's Disease Neuroimaging Initiative (ADNI) (n = 1,615; amyloid and tau positron emission tomography).
p-tau217 diagnoses AD more accurately in early-onset than late-onset patients
Overall accuracy was high (primary area under the curve (AUC) 0.923; ADNI 0.904).
The optimal biomarker shifted from tau-centric markers in LO to Aβ42/Aβ40 in EO.
Opposing-direction associations were observed for p-tau217%, which correlated negatively with onset age in AD but positively in Non-AD cognitive impairment.
In an exploratory analysis, baseline p-tau217 was associated with longitudinal cognitive decline, numerically greater in EO though based on a small subgroup.
This cross-ethnic, cross-platform study demonstrates that the diagnostic accuracy, biomarker-clinical correlation architecture, and optimal analyte selection of plasma p-tau217 vary systematically with age at onset, most markedly for tau-related measures.
These findings challenge universal threshold paradigms and support age-stratified biomarker interpretation in clinical practice and therapeutic trial design.