Journal of the American Heart Association, Volume 15, Issue 9 , May 5, 2026. BackgroundVon Willebrand factor (VWF) and ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13) are linked to dementia risk, and limited evidence suggestsapolipoprotein E(APOE)‐ε4 alters VWF release.
This study assessed whether baseline VWF and ADAMTS13 levels predict neurodegeneration and cognitive decline and evaluated effect modification byAPOE‐ε4carriership.MethodsVanderbilt Memory and Aging Project cohort participants (n=332, 73±7 years, 59% male) completed serial blood draw, neuropsychological assessment, and brain magnetic resonance imaging over 6.4 years (range 1.4–9.7 years). Baseline plasma VWF and ADAMTS13 levels were quantified using mass spectrometry and Olink.
Fully adjusted linear mixed‐effects models relatedprotein×timeandprotein×APOE‐ε4×timeinteraction terms to longitudinal brain magnetic resonance imaging and neuropsychological outcomes.ResultsLower baseline ADAMTS13 predicted faster declines in language (β=0.11,P=0.01), information processing speed (β=0.27,P=0.001), executive function (β=0.01,P=0.03), episodic memory (β=0.01,P=0.03), and visuospatial ability (β=0.11,P=0.001) and faster increases in global (β=−0.29,P=0.01) and frontal (β=−0.17,P=0.01) white matter hyperintensity volumes. Associations between ADAMTS13 and faster rates of cognitive decline and white matter injury were driven byAPOE‐ε4 carriers.
Models relating VWF to longitudinal outcomes were null.APOE‐ε4 interacted with VWF on longitudinal gray matter volumetric outcomes, such that faster rates of global gray matter atrophy were observed with higher baseline VWF levels amongAPOE‐ε4 noncarriers only (β=−1530.5,P<0.001).ConclusionsADAMTS13 shows promise as a potential plasma biomarker for brain aging outcomes, but additional research is warranted to understand the performance of VWF in the presence versus absence of anAPOE‐ε4 allele.
Journal of the American Heart Association published a clinical update in Cardiology on 20 Apr 2026. The item focuses on Plasma von Willebrand Factor and ADAMTS13 Interact With APOE‐ε4 in Predicting Longitudinal Brain Atrophy and Cognitive Decline Over a 9‐Year Follow‐Up. Open the detail page to review the full original feed content.