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Abstract Details

Relationships Between Regional Burden of Tau Neuropathology and Age at Death and Disease Duration in Patients with Progressive Supranuclear Palsy
Movement Disorders
S26 - Movement Disorders: Basic Science (3:54 PM-4:06 PM)

A definitive diagnosis of PSP can only be established through neuropathological evaluations where four cardinal tau immunoreactive lesions are identified: globose neurofibrillary tangles; threads; tufted astrocytes and coiled bodies. It is unknown whether regional tau burden at death is associated with disease duration or age at death.

To investigate the relationship between the burden of tau pathology in neurons, astrocytes, and oligodendroglia in different brain regions and disease duration and age at death in patients with progressive supranuclear palsy (PSP).

From a cohort of 190 PSP patients recruited by the Neurodegenerative Research Group (NRG) at Mayo Clinic, Minnesota between 2009-2023, we identified 45 patients who had died and underwent histopathological evaluation. All patients were clinically categorized as PSP-Subcortical or PSP-Cortical based on presenting signs/symptoms. We performed semi-quantitative lesion count for each of the four cardinal lesions across 10 brain regions: cerebellar dentate, midbrain tegmentum, substantia nigra, subthalamic nucleus, red nucleus, globus pallidus, ventral thalamus, striatum, superior frontal, and precentral cortices. We fit Bayesian linear hierarchical regression models to estimate the relationship between total pathological burden (y) and either disease duration (x) or age at death (x) by region.

Of the 45 patients, 18 (40%) were female and 26 (58%) were classified as PSP-Subcortical. The median (IQR) age at death was 75 (56–87) years with median disease duration of 8 (6–10) years. Younger age at death was associated with greater total tau burden in the pallidum, red nucleus, striatum, and subthalamic nucleus (all p≤0.01) while shorter disease duration was associated with greater total tau burden in the red nucleus (p=0.05). The observed patterns were generally similar in both the PSP-Cortical and PSP-Subcortical groups.

The results suggest that higher burden of tau pathology in specific subcortical regions in PSP is associated with greater mortality.

Negin Badihian (Mayo Clinic)
Dr. Badihian has nothing to disclose.
No disclosure on file
No disclosure on file
Farwa Ali (Mayo Clinic) Dr. Ali has nothing to disclose.
Hugo Botha (Mayo School of Graduate Medical Education, Rochester) Dr. Botha has received research support from NIH.
No disclosure on file
No disclosure on file
Rodolfo Savica (Mayo Clinic) The institution of Dr. Savica has received research support from ACADIA Pharmaceuticals, Inc.
Dennis Dickson (Mayo Clinic) Dr. Dickson has nothing to disclose.
Jennifer Whitwell (Mayo Clinic) Dr. Whitwell has nothing to disclose.
Keith Josephs (Mayo Clinic) Dr. Josephs has nothing to disclose.