2024 American Academy of Neurology Abstract Website

Negin Badihian¹, Nirubol Tosakulwong², Stephen Weigand², Farwa Ali¹, Hugo Botha¹, Heather Clark¹, Julie Stierwalt¹, Rodolfo Savica¹, Dennis Dickson³, Jennifer Whitwell⁴, Keith Josephs¹
¹Department of Neurology, Mayo Clinic, Rochester, MN, USA., ²Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., ³Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., ⁴Department of Radiology, Mayo Clinic, Rochester, MN, USA.

Objective:

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).

Background:

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.

Design/Methods:

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.

Results:

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.

Conclusions:

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