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

Daniel D Callow1, Nisha Rani1, Kylie H Alm1

  • 1Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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

Hippocampal microstructure changes, measured by diffusion-weighted imaging (DWI), are linked to tau pathology and memory decline in amyloid-positive individuals, suggesting early Alzheimer's disease (AD) detection. These microstructural changes fully mediate the relationship between tau PET burden and memory performance in early AD stages.

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Area of Science:

  • Neuroimaging
  • Neurodegeneration
  • Alzheimer's Disease Research

Background:

  • Hippocampal gray matter microstructure assessed via diffusion-weighted imaging (DWI) is a sensitive marker for neurodegeneration in Alzheimer's disease (AD).
  • Microstructural changes in the hippocampus may precede volumetric loss, providing insights into early AD pathogenesis.
  • Amyloid-beta (Aβ) and tau pathologies are key hallmarks of AD, influencing neurodegeneration and cognitive decline.

Purpose of the Study:

  • To investigate the relationship between hippocampal microstructure (DWI), tau pathology (PET), and episodic memory.
  • To examine the moderating role of amyloid-beta (Aβ) status on these associations.
  • To determine if tau PET burden mediates the link between hippocampal microstructure and memory performance in individuals with varying Aβ status.

Main Methods:

  • The study included 192 participants without dementia (14 with mild cognitive impairment [MCI]), with Aβ status determined by PET imaging.
  • Multiple linear regression analyses were used to test for interactions between Aβ status, hippocampal mean diffusivity (MD), and tau PET burden.
  • Episodic memory performance was assessed using a composite score.

Main Results:

  • Increased hippocampal MD was associated with worse memory and greater tau PET burden, but only in amyloid-positive individuals.
  • Amyloid-beta status significantly moderated the associations between hippocampal MD, tau PET, and memory.
  • Tau PET burden fully mediated the relationship between elevated hippocampal MD and poorer memory performance in amyloid-positive participants, independent of hippocampal volume.

Conclusions:

  • Hippocampal microstructure is sensitive to AD-related pathological burden and neurodegeneration, particularly in the early symptomatic stages.
  • These findings highlight the interplay between Aβ status, tau pathology, hippocampal microstructure, and cognitive decline in early AD.
  • DWI assessment of hippocampal microstructure may serve as a valuable biomarker for early AD detection and progression monitoring.