Biomarkers.

Alzheimers Dement

Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.

Published: December 2024

Background: In-vivo detection of neuropathology is critical for early diagnosis of neurodegenerative diseases. Post-mortem brain magnetic resonance imaging (MRI) of pathological protein inclusions could further our ability to detect them in vivo and correlate MRI parameters to histopathological substrates. In this post-mortem study, we aimed to identify MRI correlates of neurodegenerative disease pathology in a brain with various forms of proteinopathies.

Method: One large cortical section containing the temporal cortex, hippocampus and thalamus was used from an 82-year-old male patient, with chronic traumatic encephalopathy (CTE), Alzheimer's disease (AD), TDP-43, aging related tau astrogliosis (ARTAG) and cerebral amyloid angiopathy (CAA) pathologies. The post-mortem tissue sample was scanned using high-resolution Rapid Acquisition with Relaxation Enhancement (RARE) and multi-gradient echo (MGE) sequences on an 11.7 Tesla MRI (Bruker, Germany). RARE scan parameters were as follows: field of view: 97.2 x 86.4 x 28.8 mm, rep time: 2 s, RARE factor: 8, echo time: 48 ms, echo spacing: 12 ms, 225 μm isotropic resolution. Tissue samples were subsequently sectioned (0.004 mm thick slices) and stained using AT8 - for Tau, GFAP - for astrogliosis and H&E/Luxol - for distinguishing gray (GM) and white matter (WM) and PERLS - for extracellular iron.

Result: Post-mortem MRI allowed for clear visualization of WM and GM structures. Decreased cell density in WM as visualised on H&E stained slices was associated with hyperintensities on T2w images and decreased measured R2*. AT8 immunoreactivity in GM and WM was associated with hyperintensities on T2w images and decreased measured R2*.

Conclusion: High-resolution MRI of post-mortem tissue allowed for visualization of fine WM-GM details, as well as hyperintensities in areas that potentially correspond to increased densities of tau pathology and decreased WM density. Further studies are needed to investigate the potential for high-resolution post-mortem MRI to visualize the pathological process in neurodegenerative diseases.

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http://dx.doi.org/10.1002/alz.092362DOI Listing

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