Evaluation of an in vivo biomarker of arteriolosclerosis (ARTS) and its associations with cognition and multimodal ATN(V) biomarkers in a cardiometabolic-risk enriched community cohort

ObjectiveTo evaluate associations between an in vivo (MRI) marker of arteriolosclerosis (ARTS) and multimodal neuroimaging and plasma ATN(V) biomarkers. MethodsAmong 238 participants with both amyloid and tau PET scans within one year of MRI, we examined multivariable adjusted models relating ARTS with structural MRI (cortical thickness/volume, white matter hyperintensities [WMH]), diffusion MRI (fractional anisotropy [FA], mean diffusivity [MD], NODDI free water [FW]), cerebral blood flow, plasma biomarkers (p-tau217, A{beta}42/40, neurofilament light, glial fibrillary acidic protein [GFAP]), and PET imaging. ResultsAs expected, ARTS was most strongly linked to age and greater WMH burden and diffusion-based indices of microstructural disruption (FA, MD, FW). ARTS was elevated in ATN biomarker-positive groups (highest in A+T+N+) and was associated with greater neurodegeneration and higher plasma biomarker levels, GFAP in particular. ConclusionsARTS relates to other markers of vascular brain injury, neurodegeneration, amyloid and tau pathology within the ATN(V) framework, and inflammation. HighlightsO_LIARTS scores are elevated in ATN-positive individuals, most prominently in A+T+N+ C_LIO_LIARTS may exert stage-specific effects on neurodegeneration rather than track A/T burden. C_LIO_LIStrong ARTS-GFAP association suggests role of astroglial activation in vascular-related neurodegeneration C_LIO_LIFindings underscore the importance of vascular contributions to AD/ADRD pathophysiology, especially in high-cardiometabolic-risk populations C_LI