Relationships between neuronal loss, age of death, disease duration and MRI brain volumes in progressive supranuclear palsy

Abstract

Background

Neuronal loss and the presence of tau lesions in specific brain regions is required for a definitive diagnosis of progressive supranuclear palsy (PSP). We previously found tau burden in basal ganglia and red nucleus to be associated with disease duration and age at death. It is currently unknown whether neuronal loss is also associated with disease duration and age at death, or with antemortem brain volume loss in PSP.

Objective

To investigate whether neuronal loss is associated with tau burden, age at death, disease duration, or brain volume loss in PSP.

Methods

Forty-one pathologically confirmed PSP participants prospectively recruited and followed by the Neurodegenerative Research Group (NRG), Mayo Clinic, MN, between 2009 and 2023, of which 40 completed antemortem MRI, were analyzed. Neuronal loss in the subthalamic and red nuclei was determined on hematoxylin and eosin. Multinomial logistic regressions with age at death, disease duration, and brain volume as independent variables, and regional neuronal loss as outcome, were performed.

Results

Fourteen participants (34 %) were female, median age at death was 74 years [68, 79], and median disease duration was 8.2 years [5.7, 9.9]. Greater neuronal loss was associated with greater burden of glial, but not neuronal, tau lesions in both nuclei. Greater neuronal loss was associated with shorter disease duration in both nuclei, particularly in the subthalamic nucleus, and smaller volume on MRI of the red nucleus.

Conclusions

Neuronal loss in subthalamic and red nuclei, cardinal PSP regions, appear to be playing a role in disease duration and brain volume loss in PSP.