Introduction: Amyloid beta (Aβ) accumulation is the first pathological hallmark of Alzheimer’s disease (AD), and it is associated with altered white matter (WM) microstructure. We aimed to investigate this relationship at a regional level in a cog-nitively unimpaired cohort. Methods: We included 179 individuals from the European Medical Information Framework for AD (EMIF-AD) preclinAD study, who underwent diffusion magnetic resonance (MR) to determine tract-level fractional anisotropy (FA); mean, radial, and axial diffusivity (MD/RD/AxD); and dynamic [18F]flutemetamol) positron emission tomogra-phy (PET) imaging to assess amyloid burden. Results: Regression analyses showed a non-linear relationship between regional amyloid burden and WM microstructure. Low amyloid burden was associated with increased FA and decreased MD/RD/AxD, followed by decreased FA and increased MD/RD/AxD upon higher amyloid burden. The strongest association was observed between amyloid burden in the precuneus and body of the corpus callosum (CC) FA and diffusivity (MD/RD) measures. In addition, amyloid burden in the anterior cingu-late cortex strongly related to AxD and RD measures in the genu CC. Discussion: Early amyloid deposition is associated with changes in WM microstruc-ture. The non-linear relationship might reflect multiple stages of axonal damage.
Original languageEnglish
Article numbere12124
Pages (from-to)e12124
JournalAlzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Issue number1
Publication statusPublished - 2021

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