Postmortem brain MRI reveals differential associations of subcortical and limbic volumes with cortical thinning and neuropathology patterns

Khandelwal, P.; Duong, M. T.; Levorse, L. M.; Trotman, W.; Bahena, A.; Lim, S. A.; Denning, A. E.; Chung, E.; Olm, C. A.; Radhakrishnan, H.; Ittyerah, R.; Prabhakaran, K.; Mizsei, G.; Schuck, T.; Emrani, S.; Vizcarra, J. A.; Robinson, J.; Ohm, D. T.; Phillips, J. S.; Cohen, J.; Wisse, L. E. M.; Detre, J. A.; Nasrallah, I. M.; Brown, C. A.; Das, S. R.; Lee, E. B.; Tisdall, M. D.; Irwin, D. J.; McMillan, C. T.; Wolk, D. A.; Yushkevich, P. A.

doi:10.64898/2025.12.30.697140

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bioRxiv · 10.64898/2025.12.30.697140

Postmortem brain MRI reveals differential associations of subcortical and limbic volumes with cortical thinning and neuropathology patterns

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Structured AbstractO_ST_ABSIntroductionC_ST_ABSThe impact of different neuropathologies on deep brain structures remains to be understood. We examine subcortical and limbic volumetry in neurodegenerative diseases involving p-tau, -synuclein and TDP-43. MethodsWe acquired neuropathological measures and brain segmentations from postmortem analysis of 132 donors with Alzheimers disease (AD), Lewy body disease (LBD), Frontotemporal Lobar Degeneration with TDP-43 (FTLD-TDP) and FTLD-Tau. ResultsLBD had the least subcortical, limbic and cortical atrophy compared to AD, FTLD-TDP and FTLD-Tau. In donors with both AD and LBD pathologies, primary LBD was associated with less atrophy than primary AD. While AD had cortico-subcortical and cortico-limbic morphometric associations, LBD had more limited parieto-occipital cortico-limbic associations. FTLD-TDP had cortico-subcortical while FTLD-Tau had cortico-subcortical and cortico-limbic associations. In AD and FTLD-Tau, hippocampal volumes correlated with p-tau burden, neuron loss and gliosis. In LBD, thalamic -synuclein severity was associated with subcortical/limbic volumes. DiscussionPostmortem neuroimaging reveals disease- and region-specific structure-pathology relationships.

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Khandelwal, P., Duong, M. T., Levorse, L. M., Trotman, W., Bahena, A., Lim, S. A., Denning, A. E., Chung, E., Olm, C. A., Radhakrishnan, H., Ittyerah, R., Prabhakaran, K., Mizsei, G., Schuck, T., Emrani, S., Vizcarra, J. A., Robinson, J., Ohm, D. T., Phillips, J. S., Cohen, J., Wisse, L. E. M., Detre, J. A., Nasrallah, I. M., Brown, C. A., Das, S. R., Lee, E. B., Tisdall, M. D., Irwin, D. J., McMillan, C. T., Wolk, D. A., Yushkevich, P. A.. 2025-12-31. Postmortem brain MRI reveals differential associations of subcortical and limbic volumes with cortical thinning and neuropathology patterns. https://doi.org/10.64898/2025.12.30.697140

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