Brain diffusivity modifies plasma pTau217 links to pathology
In 602 discovery and 2,313 validation participants, associations between plasma pTau217 and brain pathology were stronger among people with lower periventricular diffusivity.
Research Square
In an observational discovery-validation preprint examining 602 ADNI participants and 2,313 HABS-HD participants, researchers assessed whether MRI-derived periventricular diffusivity modifies associations between plasma pTau217 and Alzheimer pathology. In ADNI, pTau217 associations with amyloid Centiloid (interaction β = -0.096, 95% CI -0.154 to -0.037) and meta-temporal tau PET (β = -0.092, 95% CI -0.158 to -0.027) were stronger at lower periventricular diffusivity. Among participants with high pTau217, low diffusivity was linked to faster cognitive decline than high diffusivity, showing a difference of -0.100 Preclinical Alzheimer Cognitive Composite units per year (95% CI -0.161 to -0.038). In HABS-HD, researchers replicated the amyloid interaction (β = -0.109, 95% CI -0.147 to -0.070) and multiple tau PET interactions, with the high-pTau217 and low-diffusivity group again declining faster by -0.037 units per year.
Why it matters
Evaluating how structural brain diffusion interacts with circulating biomarkers may help refine how blood tests track neurodegenerative pathology during aging. Contextualizing plasma markers with imaging may clarify discrepancies seen between fluid measures and brain scans.
Caveats
Because of the observational design, this study cannot determine causal mechanisms, clinical decision thresholds, or real-world utility, and periventricular diffusivity serves only as an indirect marker. The findings are reported in a preprint that has not yet undergone peer review.
The paper
The Second Affiliated Hospital of Wannan Medical University
Research Square · 10 Sep 2026 · Preprint, not peer-reviewed