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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 and tau pathology, impacting cognitive decline. This highlights the critical role of neuroinflammation in AD pathogenesis.

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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 an in-vivo marker of neuroinflammation, detectable in WM via PET imaging.
  • Investigating WM inflammation's role is crucial for understanding AD beyond grey matter pathology.

Purpose of the Study:

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

Main Methods:

  • Eighty-eight participants underwent diffusion MRI, TSPO-PET, amyloid-PET, tau-PET, and plasma biomarker analysis.
  • TSPO standardized uptake value ratios were used to quantify inflammation in normal-appearing WM.
  • Associations between WM TSPO signal, AD biomarkers (amyloid, tau, GFAP, NfL), diffusion metrics, and cognition were analyzed.

Main Results:

  • A significant three-way interaction between amyloid, GM TSPO, and WM TSPO influenced tau levels.
  • Higher occipital WM TSPO, in the presence of amyloid, was associated with increased tau accumulation.
  • WM TSPO signal correlated with plasma GFAP and reduced white matter integrity, modulating amyloid's effect on cognition.

Conclusions:

  • Posterior WM inflammation, quantified by TSPO-PET, modulates the amyloid-tau relationship and its cognitive consequences.
  • These findings underscore the significance of WM inflammation in AD pathogenesis, independent of GM inflammation.
  • Targeting WM inflammation may offer new therapeutic strategies for Alzheimer's disease.