Objective: To elucidate whether the severity and distribution of tau pathology reflect the clinical presentations in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD).

Background: PSP and CBD are progressive neurodegenerative diseases characterized by the accumulation of tau proteins in both neuronal and glial cells in the gray and white matter of the neocortex, basal ganglia, diencephalon, and brainstem. Despite the similarity of neuropathology, PSP and CBD are considered distinct tauopathies. Tufted astrocytes are pathologic hallmarks of PSP, while astrocytic plaques are exclusively seen in CBD. Clinical presentations of PSP and CBD are heterogeneous, exemplified by Richardson syndrome (RS), corticobasal syndrome (CBS), frontotemporal dementia (FTD). Thus, it is challenging to predict underlying pathology based on clinical presentations.

Method: We reviewed clinical presentations and underlying pathology of 983 autopsy-confirmed PSP and 178 CBD brains. The severity of tau pathology, including neurofibrillary tangles, pretangles, coiled bodies, tufted astrocytes in PSP or astrocytic plaques in CBD, and threads was graded semi-quantitatively on a four-point scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe) in 8 brain regions: inferior temporal gyrus, motor cortex, caudate, globus pallidus, subthalamic nucleus, red nucleus, substantia nigra, and midbrain tectum. Concurrent pathologies, including Alzheimer’s disease and argyrophilic grain disease, were also assessed. Cluster analysis was performed based on the topographical distribution and severity of tau pathology. Demographics, clinical presentation, co-pathologies, were compared among the clusters.

Results: The cluster analysis divided all cases into three clusters. Cluster 1 consists of 170 CBD and 2 PSP cases; Cluster 2 consists of 3 CBD and 241 PSP cases; and Cluster 3 consists of 5 CBD and 740 PSP cases. Clinical presentations of each clusters were as follows: RS (45%), CBS (32%), and FTD (8%) in Cluster 1; RS (82%), CBS (6%), and FTD (1%) in Clusters 2; and RS (84%), CBS (6%), and FTD (1%).

Conclusion: The distribution and severity of 8 brain regions were distinct between PSP and CBD. In contrast, clinical presentations were heterogeneous within the cluster, indicating that the severity and distribution of tau pathology were insufficient to predict clinical presentations.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-severity-and-distribution-of-tau-pathology-distinguish-corticobasal-degeneration-and-progressive-supranuclear-palsy/