Layer-Dependent Effect of Aβ-Pathology on Cortical Microstructure With Ex Vivo Human Brain Diffusion MRI at 7 Tesla

Area of Science:

• Neuroimaging
• Neuropathology
• Alzheimer's Disease Research

Background:

• Alzheimer's disease (AD) pathology, including amyloid-beta (Aβ) and Tau deposition, shows known laminar-specific distribution in the neocortex.
• Direct human evidence linking AD pathology to alterations in cortical microstructure remains limited.

Purpose of the Study:

• To investigate the effects of AD neuropathology on human cortical microstructure using advanced MRI techniques.
• To correlate in vivo MRI findings with ex vivo neuropathologic measures across cortical layers.

Main Methods:

• High-resolution T2-weighted and diffusion-weighted MRI (dMRI) were performed on 15 ex vivo whole-hemisphere human brain specimens.
• Specimens included cases with low AD neuropathologic change, primary age-related tauopathy (PART), and healthy controls (HCs).
• Diffusion tensor modeling was used to analyze microstructural patterns in six cortical gray matter layers, followed by MRI-histology correlation.

Main Results:

• Amyloid-beta (Aβ)-positive cases showed higher diffusivity than Aβ-negative cases (PART and HC) in specific regions, notably the inferior frontal cortex.
• Both Aβ/Tau deposition and dMRI markers exhibited distinct layer-dependent and region-specific patterns.
• Increased diffusivity strongly correlated with Aβ burden across all six cortical layers, but not with Tau burden. Mean diffusivity in layer V of the inferior frontal cortex increased with amyloid stage.

Conclusions:

• Amyloid-beta (Aβ) pathology exerts a layer-dependent effect on human cortical microstructure.
• Diffusion MRI markers show a significant correlation with Aβ burden, particularly in specific cortical layers and regions.
• These findings suggest that dMRI-based microstructural changes may serve as a valuable biomarker for early-stage Alzheimer's neuropathologic change.