ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Combined use of plasma p-tau217, NfL, and GFAP predicts domain-specific cognitive decline in cognitively unimpaired and MCI individuals.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Review
- Sex-specific associations between astrocytic reactivity and cognitive decline in unimpaired elderly.bioRxiv : the preprint server for biology · 2026Article
- Blood-Based Biomarkers Predict Differential Longitudinal Decline in Alzheimer's Disease Psychosis: Evidence from Two Cohorts.medRxiv : the preprint server for health sciences · 2026Article
- Correlation analysis of positive Alzheimer's disease plasma biological markers with plasma immune cell and clinical characteristics in mild cognitive impairment patients in China.BMC immunology · 2026Article
- Plasma pTau217 as a Prognostic, Monitoring, and Risk-Stratification Biomarker of Clinical Progression in Lewy Body Disease.medRxiv : the preprint server for health sciences · 2026Article
- From seeds to symptoms: the molecular landscape of tau seeding in Alzheimer's disease.Frontiers in neuroscience · 2026Review
- Anemia, iron deficiency, and blood biomarkers for Alzheimer disease: clinical interpretation and dementia risk stratification.Frontiers in nutrition · 2026Review
- Combined use of plasma p-tau217, NfL, and GFAP predicts domain-specific cognitive decline in cognitively unimpaired and MCI individuals.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Plasma GFAP and language-network tau mediate the effect of amyloid burden on semantic fluency: A mediation analysis.Alzheimer's & dementia (Amsterdam, Netherlands)Article
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Authors and funding
8 authors.
Funding
Abstract
introductionAccurate identification of individuals at risk for cognitive decline is critical for treatment planning and trial enrichment strategies. We evaluated the combined utility of plasma phosphorylated tau at threonine 217 (p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in predicting domain-specific cognitive decline.
methodsParticipants (n = 523; 40.9% cognitively unimpaired [CU]; 59.1% mild cognitive impairment [MCI]) were from the Massachusetts Alzheimer's Disease Research Center. Cognition was assessed using the National Alzheimer's Coordinating Center Uniform Data Set. Participants were classified as high(+)/low(-) for each biomarker using Gaussian mixture models.
resultsAmong all participants, high p-tau217 alone [p-tau217(+)NfL(-)GFAP(-)] was associated with a steeper decline in episodic/semantic memory and processing speed compared to the all-low group (p ≤ 0.02). With the addition of high GFAP [p-tau217(+)NfL(-)GFAP(+)], steeper decline extended to most cognitive domains, including global cognition and executive function, compared to the all-low group. In CU, faster decline in global cognition and executive function was seen when all biomarkers were elevated ([p-tau217(+)NfL(+)GFAP(+)]; p ≤ 0.04). DISCUSSION: Combined plasma biomarkers predict decline in cognitive domains vulnerable to early disease. HIGHLIGHTS: High phosphorylated tau at threonine 217 (p-tau217) alone was associated with declines in semantic/episodic memory, whereas its combination with elevated glial fibrillary acidic protein (GFAP) predicted declines in a wider range of cognitive domains. Elevated neurofilament light chain (NfL) amplifies the cognitive decline already driven by p-tau217 and GFAP. In cognitively unimpaired individuals, subtle domain-specific cognitive declines can be detected when both core and non-core Alzheimer's disease biomarkers are used. Our finding highlights the importance of focusing on vulnerable cognitive domains during early disease where global cognition may appear stable but specific impairments can be masked within composite scores.
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