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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Julie Ottoy1, Min Su Kang2, Eric Yin1

  • 1LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

White matter inflammation, measured by TSPO-PET, influences Alzheimer's disease (AD) progression by modulating the relationship between amyloid-beta plaques, tau tangles, and cognitive decline, independent of grey matter inflammation.

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Area of Science:

  • Neuroimaging
  • Neuroinflammation
  • Alzheimer's Disease Pathogenesis

Background:

  • White matter (WM) inflammation is a key driver of Alzheimer's disease (AD) progression.
  • Translocator protein (TSPO) is a marker of glial inflammation, detectable in WM via PET imaging.
  • Investigating WM inflammation's role in AD is crucial for understanding disease mechanisms.

Purpose of the Study:

  • To assess the impact of WM glial inflammation, quantified by TSPO-PET, on AD biomarkers and cognitive decline.
  • To differentiate the effects of WM inflammation from grey matter (GM) inflammation in AD.
  • To explore the relationship between WM TSPO signal, AD pathology, and cognitive function across the AD spectrum.

Main Methods:

  • Eighty-eight participants underwent diffusion MRI, TSPO-PET, amyloid-PET, and tau-PET scans, along with plasma biomarker analysis (Aβ42/40, ptau181, ptau231, GFAP, NfL).
  • WM inflammation was assessed using TSPO standardized uptake value ratios in normal-appearing WM.
  • Statistical models examined associations between WM TSPO, AD biomarkers, diffusion metrics, and cognition, adjusting for confounders.

Main Results:

  • A significant three-way interaction was found between amyloid, GM TSPO, and WM TSPO on tau pathology.
  • Higher occipital WM TSPO, in the presence of amyloid, was associated with increased tau accumulation.
  • Occipital WM TSPO correlated with elevated plasma GFAP and reduced white matter integrity, and modulated cognitive performance related to amyloid and tau.

Conclusions:

  • Posterior WM inflammation, detected by TSPO-PET, plays a significant role in modulating the interplay between amyloid, tau, and cognitive impairment in AD.
  • These findings underscore the importance of white matter inflammation in AD pathogenesis, extending beyond grey matter involvement.
  • Targeting WM inflammation may offer a novel therapeutic strategy for Alzheimer's disease.