Postmortem brain MRI reveals differential associations of subcortical and limbic volumes with cortical thinning and
Pulkit Khandelwal1,2, Michael Tran Duong1, Lisa M Levorse1
1University of Pennsylvania, Philadelphia, PA, USA.
Introduction:
The 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, α-synuclein and TDP-43.
Methods:
We acquired neuropathological measures and brain segmentations from postmortem analysis of 132 donors with Alzheimer's 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).
Results:
In 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 α-synuclein severity was associated with subcortical and limbic volumes. In FTLD-TDP, TDP-43 load had no such significant associations.
Discussion:
Postmortem neuroimaging reveals unique structure-structure and structure-pathology relationships across regions and diseases.
