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.
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.
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.
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).

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.

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This post is Copyright: Jesse C. DeSimone,
Wei‐en Wang,
David A. Loewenstein,
Ranjan Duara,
Glenn E. Smith,
Karen N. McFarland,
Melissa J. Armstrong,
Darren M. Weber,
Warren Barker,
Stephen A. Coombes,
David E. Vaillancourt | March 5, 2024

Wiley: Alzheimer’s & Dementia: Table of Contents