Postmortem brain MRI reveals differential associations of subcortical and limbic volumes with cortical thinning and neurodegenerative pathologies

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INTRODUCTION: The impact of different neuropathologies on deep brain structures remains to be understood. We examine subcortical and limbic volumetry in neurodegenerative diseases involving phosphorylated tau (p-tau), α-synuclein, and transactive response DNA binding protein 43 (TDP-43). METHODS: We acquired neuropathological measures and brain segmentations from postmortem analysis of 132 donors with Alzheimer's disease (AD), Lewy body disease (LBD), frontotemporal lobar degeneration with TDP-43 (FTLD-TDP), and FTLD-tau. RESULTS: LBD 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 α-synuclein severity was associated with subcortical/limbic volumes. DISCUSSION: Postmortem neuroimaging reveals disease- and region-specific structure-pathology relationships.

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