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.
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IntroductionThe impact of different neuropathologies on deep brain structures remains to be understood. Here, we distinguish 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; n=60), Lewy body disease (LBD; n=26), Frontotemporal Lobar Degeneration with TDP-43 (FTLD-TDP; n=21) and FTLD-Tau (n=25). ResultsIn FTLD-TDP and FTLD-Tau, thalamus and striatum volumes were lower than in AD or LBD. While AD had diffuse cortico-subcortical and cortico-limbic morphometric associations, LBD had more limited parieto-occipital cortico-limbic associations. FTLD-TDP had cortico-subcortical associations while FTLD-Tau had 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 and limbic volumes. In FTLD-TDP, TDP-43 load had no such significant associations. DiscussionPostmortem neuroimaging reveals unique structure-structure and structure-pathology relationships across regions and diseases. Highlights[bullet] FTLD-Tau and FTLD-TDP show lower thalamic and striatal volumes than AD or LBD groups. [bullet]Subcortical and limbic volume loss significantly correlates with global brain shrinkage in AD. [bullet]LBD exhibits less postmortem subcortical and limbic atrophy compared to other groups. Parieto-occipital atrophy corresponds to limbic but not subcortical volume loss in LBD. [bullet]FTLD-Tau has cortico-limbic morphometric associations while FTLD-TDP has cortico-subcortical associations. [bullet]In AD and FTLD-Tau, hippocampal volume correlates with p-tau load, neuronal loss and gliosis semiquantitative measures. [bullet]In LBD, thalamic -synuclein burden is associated with subcortical and limbic volumes. [bullet]In FTLD-TDP, TDP-43 pathology burden shows no significant volume associations.
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