Authors
Menghan Liu, Katherine Gong, Yike Chen, Gyujin Heo, Ying Xu, Jigyasha Timsina, Daniel Western, John Budde, John C Morris, Giorgetti Marco, David M Holtzman, Jeremiah Hinson, Scott Levin, Nicholas Ashton, Marisa Denkinger, Suzanne E Schindler, Kausik Das, Muhammad Ali, Carlos Cruchaga
Published in
Alzheimer's & dementia : the journal of the Alzheimer's Association. Volume 22. Issue 8. Pages e71748.
Abstract
We recently identified a plasma-based seven-protein model with strong performance for Alzheimer's disease (AD) classification. Here, we evaluated whether these proteins, alone or combined with plasma phosphorylated tau 217 (p-tau217), predict progression from cognitively unimpaired to symptomatic AD.
Using longitudinal data from Knight-ADRC (Alzheimer's Disease Research Center) with replication in Alzheimer's Disease Neuroimaging Initiative (ADNI), we modeled time to progression using Cox regression. Models included p-tau217, the seven-protein panel, and their combination.
The p-tau217 alone showed similar progression prediction (hazard ratio [HR] = 4.08) than the seven-protein model (HR = 4.85). Integrating the seven-protein model with ptau217 significantly improved risk, identifying a high-risk group (HR = 11.15) with two intermediate-risk groups. Simplified models retained prognostic value, with top-performing ratios, Complexin-2/Synaptic vesicle membrane protein VAT-1 homolog (CPLX2/VAT1) and Acetylcholinesterase/Neuronal pentraxin receptor (ACHE/NPTXR) also lead to a significantly better risk stratification than p-tau217 alone.
Integrating p-tau217 with targeted plasma proteins enables graded risk stratification and identifies individuals at highest risk of progression, supporting clinically scalable approaches for early risk assessment.
PMID:
42598783
Bibliographic data and abstract were imported from PubMed on 14 Aug 2026.
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