COMBINED IMPACT OF PLASMA PHOSPHO-TAU 217, GFAP AND NFL ON LONGITUDINAL DOMAIN-SPECIFIC COGNITIVE DECLINE - Research Article Abstract

Q: Which plasma biomarkers are evaluated and what do they represent?

The study assesses plasma p-tau217, NfL, and GFAP. p-tau217 is linked to tau pathology, NfL reflects axonal damage and neurodegeneration, and GFAP indicates inflammation.

Q: How were participants stratified and how were cognitive trajectories analyzed?

Participants were stratified by high/low plasma levels of p-tau217, NfL, and GFAP. Linear mixed-effects models across 8 biomarker groups predicted cognitive trajectories over 7 years while controlling for age, sex, and education.

Q: What is the main finding about the combined biomarker effects?

High p-tau217 alone associated with declines in Logical Memory and Boston Naming, while significant declines in CDR sum of box and MMSE required combination with high NfL and/or GFAP. Neither high GFAP alone nor high NfL alone showed significant cognitive declines.

Sep 29, 2026

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Clinical trials increasingly target pre-manifest and early Alzheimer’s disease, where accurate prediction of clinical progression is crucial for avoiding unnecessary treatment and improving trial efficiency. The study evaluates plasma p-tau217, NfL, and GFAP as diagnostic and prognostic biomarkers reflecting tau pathology, axonal damage/neurodegeneration, and inflammation. Using trajectories from 523 participants over 7 years, high p-tau217 showed domain-specific declines in Logical Memory and Boston Naming, especially when combined with high NfL and/or GFAP.

LanguageEnglish

CategoryResearch & Report

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Abstract

Biomarkers and rationale

Study design and cognitive measures

Key findings and combined effects

Conclusion

940 Innovation in Aging, 2025, Vol. 9, No. S2 Abstract citation ID: igaf122.3176 COMBINED IMPACT OF PLASMA PHOSPHO-TAU 217, GFAP AND NFL ON LONGITUDINAL DOMAIN-SPECIFIC COGNITIVE DECLINE Chao-Yi Wu1, Liu Chen1, Jennifer Gatchel2, Sudeshna Das1, Pia Kivisäkk2, Steven Arnold2, and Hiroko Dodge1, 1. Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States, 2. Massachusetts General Hospital, Boston, Massachusetts, United States Clinical trials are increasingly focused on pre-manifest and early Alzheimer’s disease. Accurately predicting clinical progression is important to avoid unnecessary treatment and improve trial efficiency. Plasma p-tau217, an indicator of tau pathology with strong associations to amyloid-beta pathology, NfL, a marker of axonal damage and neurodegeneration and GFAP, a marker of inflammation, are promising diagnostic and prognostic tools. Their combined use could offer more accurate prognostic insights than either biomarker alone. We examined the trajectories of domain-specific cognitive functions by stratifying participants based on plasma p-tau217, NfL and GFAP levels (high/ low) . Participants were from the Massachusetts Alzheimer’s Disease Research Center cohort (n = 523) . Cognitive functions were assessed using the National Alzheimer’s Coordinating Center Uniform Data Set v1-3: global cognition (CDR sum of box; MMSE, MoCA converted in v3), memory (Logical Memory), executive functions (Trail Making Test B), language (Boston Naming), and language-based executive function (Category Fluency Animals) . We used linear mixed-effects models with 8 groups combining 3 plasma biomarkers to predict cognitive trajectories over 7 years, controlling for age, sex, and education. High p-tau217 alone was significantly associated with declinesin Logical Memory (coefficient=-0.12; p = 0.03) and Boston Naming (coefficient=-0.16; p < 0.01), but not associated with decline in CDR sum of box and MMSE unless combined with a high burden of NfL and/or GFAP (CDR group*time coefficients=0.17-0.34, p <0.01; MMSE group*time coefficients=-0.39 to-0.69, p < 0.01). Neither high GFAP alone nor high NfL alone was associated with significant cognitive declines. The combined use of plasma biomarkers provides a promising approach for predicting domain-specific cognitive decline.

FAQs

Which plasma biomarkers are evaluated and what do they represent?

The study assesses plasma p-tau217, NfL, and GFAP. p-tau217 is linked to tau pathology, NfL reflects axonal damage and neurodegeneration, and GFAP indicates inflammation.

How were participants stratified and how were cognitive trajectories analyzed?

Participants were stratified by high/low plasma levels of p-tau217, NfL, and GFAP. Linear mixed-effects models across 8 biomarker groups predicted cognitive trajectories over 7 years while controlling for age, sex, and education.

What is the main finding about the combined biomarker effects?

High p-tau217 alone associated with declines in Logical Memory and Boston Naming, while significant declines in CDR sum of box and MMSE required combination with high NfL and/or GFAP. Neither high GFAP alone nor high NfL alone showed significant cognitive declines.

Sep 29, 2026

Upload by Mary Man