Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Postmortem brain MRI reveals differential associations of subcortical and limbic volumes with cortical thinning and neurodegenerative pathologies.
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Khandelwal Pulkit, Duong Michael Tran, Levorse Lisa M, Trotman Winifred, Bahena Alejandra, Lim Sydney A, Denning Amanda E, Chung Eunice, Olm Christopher A, Radhakrishnan Hamsanandini, Ittyerah Ranjit, Prabhakaran Karthik, Mizsei Gabor, Schuck Theresa, Emrani Sheina, Vizcarra Joaquin A, Robinson John, Ohm Daniel T, Phillips Jeffrey S, Cohen Jesse, Wisse Laura E M, Detre John A, Nasrallah Ilya M, Brown Christopher A, Das Sandhitsu R, Lee Edward B, Tisdall M Dylan, Irwin David J, McMillan Corey T, Wolk David A, Yushkevich Paul A
Аннотация
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.
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.