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Age-dependent diagnostic and correlational architecture of multiplex plasma biomarkers in Alzheimer's disease: a cross-ethnic, cross-platform validation study.

Overview

Authors: Boru Jin1,2,3, Aitong Li1,2,3, Fengling Xu1,2,3, Cong Chen1,2,3, Jiawen Dong1,2,3, Jingjing Wang1,2,3, Dantong Tang1,2,3, Ying Gu1,2,3, Huayan Liu1,2,3
  1. Department of Neurology, First Hospital of China Medical University, Shenyang, Liaoning Province, China
  2. Key Laboratory of Neurological Disease Big Data of Liaoning Province, Shenyang, China
  3. Shenyang Clinical Medical Research Center for Difficult and Serious Diseases of the Nervous System, Shenyang, China
Institutions: First Hospital of China Medical University (China); China Medical University (China)
Journal: Alzheimer's research & therapy, volume 18, issue 1, article 169
Dates: received 30 March 2026; accepted 11 June 2026; published online 25 June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1186/s13195-026-02119-z · PMID 42351234 · PMCID PMC13393608 · OpenAlex W7165913909
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: other (modality), PET / SPECT (modality), human (organism), Alzheimer's / dementia (population), clinical / translational (subfield)
Methods: Connectivity, Statistics
Keywords: Plasma p-tau217, Alzheimer’s disease, Early-onset, Late-onset, Age-stratified, Diagnostic accuracy, Biomarker–clinical correlation, Multiplex immunoassay, Cross-ethnic validation, ADNI
MeSH: Alzheimer Disease*, tau Proteins*, Age of Onset, Aged, Aged, 80 and over, Amyloid beta-Peptides, Biomarkers, Cohort Studies, Female, Humans, Male, Middle Aged, Positron-Emission Tomography (* major topic)
Topic: Dementia and Cognitive Impairment Research (Psychiatry and Mental health, Medicine), according to OpenAlex
Funding: Joint Program of Science and Technology Plan of Liaoning Province (2024JH2/102600308); NIA NIH HHS (U01 AG024904); Doctoral Start-up Foundation of Liaoning Province (2024-BS-038)
Citations: not cited yet (Europe PMC); 44 references in the paper

Abstract

Background: 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.

Methods: 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 (PET) reference), with validation in the Alzheimer's Disease Neuroimaging Initiative (ADNI) (n = 1,615; amyloid and tau PET). Diagnostic accuracy and biomarker–clinical correlations were compared between early-onset (EO < 65 years) and late-onset (LO ≥ 65 years) subgroups.

Results: Overall accuracy was high (primary area under the curve (AUC) 0.923; ADNI 0.904). In ADNI, p-tau217 showed higher accuracy in EO than LO (AUC 0.940 vs 0.892, P = 0.012), most pronounced at age 60 and absent by 70. The optimal biomarker shifted from tau-centric markers in LO to Aβ42/Aβ40 in EO. Tau biomarker–clinical correlations diverged sharply by onset age and were stronger in EO for cognitive and neuropsychiatric outcomes, whereas glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) showed no age-dependent heterogeneity. 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. Cross-ethnic generalizability was supported by the ADNI-Asian subgroup.

Conclusions: 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.

Supplementary Information: The online version contains supplementary material available at 10.1186/s13195-026-02119-z.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

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Data

Datasets cited

Data availability

The primary cohort data are available from the corresponding author upon reasonable request. ADNI data are publicly available at adni.loni.usc.edu.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 10 keywords, 13 MeSH terms, 3 funders, 44 references.

Cite

This paper

Jin, B., Li, A., Xu, F., Chen, C., Dong, J., Wang, J., Tang, D., Gu, Y., & Liu, H. (2026). Age-dependent diagnostic and correlational architecture of multiplex plasma biomarkers in Alzheimer's disease: a cross-ethnic, cross-platform validation study. Alzheimer's research & therapy, 18(1), 169. https://doi.org/10.1186/s13195-026-02119-z

BibTeX

@article{jin2026age,
author = {Jin, Boru and Li, Aitong and Xu, Fengling and Chen, Cong and Dong, Jiawen and Wang, Jingjing and Tang, Dantong and Gu, Ying and Liu, Huayan},
title = {{Age-dependent diagnostic and correlational architecture of multiplex plasma biomarkers in Alzheimer's disease: a cross-ethnic, cross-platform validation study}},
journal = {Alzheimer's research \& therapy},
year = {2026},
month = jun,
volume = {18},
number = {1},
pages = {169},
publisher = {BMC},
issn = {1758-9193},
doi = {10.1186/s13195-026-02119-z},
url = {https://doi.org/10.1186/s13195-026-02119-z},
pmid = {42351234},
pmcid = {PMC13393608}
}

RIS

TY - JOUR
AU - Jin, Boru
AU - Li, Aitong
AU - Xu, Fengling
AU - Chen, Cong
AU - Dong, Jiawen
AU - Wang, Jingjing
AU - Tang, Dantong
AU - Gu, Ying
AU - Liu, Huayan
TI - Age-dependent diagnostic and correlational architecture of multiplex plasma biomarkers in Alzheimer's disease: a cross-ethnic, cross-platform validation study
T2 - Alzheimer's research & therapy
J2 - Alzheimers Res Ther
PY - 2026
DA - 2026/06/25
VL - 18
IS - 1
SP - 169
SN - 1758-9193
PB - BMC
DO - 10.1186/s13195-026-02119-z
UR - https://doi.org/10.1186/s13195-026-02119-z
LA - en
ER -

CSL-JSON

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