Diffusion MRI relates to plasma Aβ42/40 in PET negative participants without dementia

Abstract INTRODUCTION Magnetic resonance imaging (MRI) biomarkers are needed for indexing early biological stages of Alzheimer's disease (AD), such as plasma amyloid‐β (Aβ42/40) positivity in Aβ positron emission tomography (PET) negative individuals. METHODS Diffusion free‐water (FW) MRI was acquired in individuals with normal cognition (NC) and mild cognitive impairment (MCI) with Aβ plasma‐/PET‐ (NC = 22, MCI = 60), plasma+/PET‐ (NC = 5, MCI = 20), and plasma+/PET+ (AD dementia = 21) biomarker status. Gray and white matter FW and fractional anisotropy (FAt) were compared cross‐sectionally and the relationships between imaging, plasma and PET biomarkers were assessed. RESULTS Plasma+/PET‐ demonstrated increased FW (24 regions) and decreased FAt (66 regions) compared to plasma‐/PET‐. FW (16 regions) and FAt (51 regions) were increased in plasma+/PET+ compared to plasma+/PET‐. Composite brain FW correlated with plasma Aβ42/40 and p‐tau181. DISCUSSION FW imaging changes distinguish plasma Aβ42/40 positive and negative groups, independent of group differences in cognitive status, Aβ PET status, and other plasma biomarkers (i.e., t‐tau, p‐tau181, glial fibrillary acidic protein, neurofilament light). Highlights Plasma Aβ42/40 positivity is associated with brain microstructure decline. Plasma+/PET‐ demonstrated increased FW in 24 total GM and WM regions. Plasma+/PET‐ demonstrated decreased FAt in 66 total GM and WM regions. Whole‐brain FW correlated with plasma Aβ42/40 and p‐tau181 measures. Plasma+/PET‐ demonstrated decreased cortical volume and thickness.