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Updated: Jan 8, 2026

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Alzheimer's Imaging Consortium.

Jeremy A Tanner1, Sophia Lu2, Hugo J Aparicio3

  • 1University of Texas Health San Antonio, San Antonio, TX, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
PubMed
Summary
This summary is machine-generated.

Plasma biomarkers like Ptau181, GFAP, and NfL show promise for detecting brain changes in the general population. Elevated Ptau181 is linked to Alzheimer's disease (AD) patterns, while GFAP and NfL indicate neurodegeneration and vascular disease severity.

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Area of Science:

  • Neuroscience
  • Biomarker Discovery
  • Population Health

Background:

  • Plasma biomarkers for Alzheimer's disease and related dementias (ADRD) are emerging but require validation in general populations.
  • The association of plasma Ptau181 with brain structure and the distinct roles of plasma NfL and GFAP in neurodegeneration versus vascular disease remain unclear in community cohorts.

Purpose of the Study:

  • To assess the association between plasma Ptau181 and brain MRI outcomes in a population-based cohort.
  • To determine if elevated plasma Ptau181 modifies the relationship between plasma NfL, GFAP, and brain MRI features.

Main Methods:

  • Utilized data from the Framingham Heart Study (FHS) Offspring and Omni 1 Cohorts, including plasma biomarkers (Ptau181, GFAP, NfL) and brain MRI.
  • Employed multivariate linear regressions adjusted for relevant covariates, with FDR correction for statistical significance.
  • Conducted sensitivity analyses excluding participants with dementia and/or stroke to ensure robustness.

Main Results:

  • Elevated plasma Ptau181 correlated with AD-pattern cortical thickness and atrophy.
  • Elevated GFAP was associated with AD-pattern atrophy in individuals with high Ptau181 and white matter hyperintensities in those with low Ptau181.
  • Elevated NfL was linked to atrophy in all participants and extensive white matter hyperintensities in those with high Ptau181.

Conclusions:

  • Plasma Ptau181, GFAP, and NfL collectively offer insights into the causes and severity of brain conditions in the community.
  • In Alzheimer's disease (AD), these biomarkers indicate worsening neurodegeneration, with NfL also reflecting vascular disease.
  • In individuals without elevated Ptau181, GFAP is associated with vascular disease, highlighting differential biomarker roles.