White matter microstructure disruption in early stage amyloid pathology

Area of Science:

• Neuroimaging
• Neuropathology
• Alzheimer's Disease Research

Background:

• Amyloid beta (Aβ) accumulation is an early pathological hallmark of Alzheimer's disease (AD).
• Aβ burden is associated with alterations in white matter (WM) microstructure.
• Understanding this relationship in cognitively unimpaired individuals is crucial for early AD detection.

Purpose of the Study:

• To investigate the regional relationship between amyloid burden and WM microstructure.
• To analyze this association in a cohort of cognitively unimpaired individuals.
• To elucidate early pathological changes in preclinical AD.

Main Methods:

• Utilized diffusion magnetic resonance imaging (dMRI) to assess WM microstructure (FA, MD, RD, AxD).
• Employed positron emission tomography (PET) imaging with [18F]flutemetamol to quantify regional amyloid burden.
• Included 179 participants from the EMIF-AD preclinAD study.

Main Results:

• A non-linear relationship was found between regional amyloid burden and WM microstructure.
• Low amyloid burden correlated with increased FA and decreased diffusivity (MD/RD/AxD).
• Higher amyloid burden was associated with decreased FA and increased diffusivity, particularly between precuneus/anterior cingulate cortex amyloid and corpus callosum microstructure.

Conclusions:

• Early amyloid deposition significantly impacts WM microstructure.
• The observed non-linear pattern may indicate distinct phases of axonal damage in early AD.
• These findings highlight the utility of neuroimaging biomarkers for detecting early AD pathology.