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Biomarkers.

Linda Zhang1, Jesús Silva-Rodríguez1, Eva Alfayate1

  • 1CIEN Foundation, Reina Sofia Alzheimer Center, ISCIII, Madrid, Madrid, Spain.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary

Elevated plasma p-tau217 levels in cognitively unimpaired individuals are associated with increased cortical mean diffusivity (MD) in Alzheimer's disease (AD) relevant regions. These findings suggest early microstructural changes detectable before cognitive decline.

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Area of Science:

  • Neuroimaging
  • Biomarkers
  • Alzheimer's Disease Research

Background:

  • Plasma p-tau217 is a reliable biomarker for early Alzheimer's disease (AD) pathology.
  • Cortical mean diffusivity (MD) from diffusion-weighted imaging may reflect early microstructural changes in neurodegenerative diseases.
  • The relationship between plasma p-tau217 and cortical MD in cognitively unimpaired individuals is unstudied.

Purpose of the Study:

  • To investigate the association between plasma p-tau217 levels and cortical mean diffusivity (MD) in cognitively unimpaired elderly individuals.
  • To determine if elevated p-tau217 is linked to microstructural changes in specific brain regions.

Main Methods:

  • Cross-sectional analysis of 1029 cognitively unimpaired elderly participants from the Vallecas Project cohort.
  • Plasma p-tau217 levels measured using the LUMIPULSE platform; participants classified as ptau217+ or ptau217-.
  • Diffusion-weighted MRI data analyzed to obtain cortical grey matter MD maps, with voxel-wise statistical analysis controlling for age and sex.

Main Results:

  • The ptau217+ group was significantly older than the ptau217- group.
  • After controlling for age and sex, the ptau217+ group exhibited significantly higher cortical MD.
  • Elevated MD was observed in bilateral medial temporal (amygdala, hippocampus) and insular regions in the ptau217+ group.

Conclusions:

  • Cortical MD changes are detectable in cognitively unimpaired individuals with elevated plasma p-tau217.
  • These observed MD changes occur in brain regions typically associated with AD neuropathology.
  • Longitudinal analysis of MD changes in this cohort is currently underway.