Correlation between clinical and neuropathological subtypes of progressive supranuclear palsy

Ryuichi Koizumi; Akio Akagi; Yuichi Riku; Hiroaki Miyahara; Jun Sone; Fumiaki Tanaka; Mari Yoshida; Yasushi Iwasaki

doi:10.1016/j.parkreldis.2024.106076

Correlation between clinical and neuropathological subtypes of progressive supranuclear palsy

Parkinsonism Relat Disord. 2024 Mar 9:106076. doi: 10.1016/j.parkreldis.2024.106076. Online ahead of print.

Authors

Ryuichi Koizumi¹, Akio Akagi², Yuichi Riku³, Hiroaki Miyahara⁴, Jun Sone⁵, Fumiaki Tanaka⁶, Mari Yoshida⁷, Yasushi Iwasaki⁸

Affiliations

¹ Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazako Karimata, Nagakute City, Aichi prefecture, 480-1103, Japan; Department of Neurology and Stroke Medicine, Graduate School of Medicine, Yokohama City University, 3-9 Fukura, Kanazawa Ward, Yokohama City, Kanagawa prefecture, 236-0004, Japan. Electronic address: t206028e@yokohama-cu.ac.jp.
² Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazako Karimata, Nagakute City, Aichi prefecture, 480-1103, Japan. Electronic address: akio.akagi@gmail.com.
³ Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazako Karimata, Nagakute City, Aichi prefecture, 480-1103, Japan. Electronic address: likuliku23@yahoo.co.jp.
⁴ Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazako Karimata, Nagakute City, Aichi prefecture, 480-1103, Japan. Electronic address: miyahara.hiroaki.926@mail.aichi-med-u.ac.jp.
⁵ Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazako Karimata, Nagakute City, Aichi prefecture, 480-1103, Japan. Electronic address: sone.jun.251@mail.aichi-med-u.ac.jp.
⁶ Department of Neurology and Stroke Medicine, Graduate School of Medicine, Yokohama City University, 3-9 Fukura, Kanazawa Ward, Yokohama City, Kanagawa prefecture, 236-0004, Japan. Electronic address: ftanaka@yokohama-cu.ac.jp.
⁷ Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazako Karimata, Nagakute City, Aichi prefecture, 480-1103, Japan. Electronic address: myoshida@aichi-med-u.ac.jp.
⁸ Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazako Karimata, Nagakute City, Aichi prefecture, 480-1103, Japan. Electronic address: iwasaki@sc4.so-net.ne.jp.

PMID: 38494398
DOI: 10.1016/j.parkreldis.2024.106076

Abstract

Introduction: Progressive supranuclear palsy (PSP) is characterized by pathology prominently in the basal ganglia, the tegmentum of the brainstem, and the frontal cortex. However, pathology varies according to clinical features. This study aimed to statistically verify the correspondence between the clinical and pathological subtypes of PSP.

Methods: We identified patients with a pathological diagnosis of PSP and classified the eight clinical subtypes of the Movement Disorders Society criteria for the clinical diagnosis of PSP (MDS-PSP criteria) into the Richardson, Akinesia, and Cognitive groups. We used anti-phosphorylated tau antibody immunostaining to semi-quantitatively evaluate neurofibrillary tangles (NFTs) and coiled bodies/threads (CB/Ths) in the globus pallidus, subthalamic nucleus, and midbrain tegmentum. In the frontal cortex, tufted astrocytes (TAs) and CB/Ths were assessed on a 3-point scale. We compared the pathology among the three groups, recorded the phenotypes ranked the second and lower in the multiple allocation extinction rule and examined whether the pathology changed depending on applying each phenotype.

Results: The Richardson group exhibited severe NFTs and CB/Ths in the midbrain tegmentum. The Akinesia group showed severe NFTs in the globus pallidus. The Cognitive group had severe TAs and CB/Ths in the frontal cortex. TAs and CB/Ths in the frontal cortex correspond to behavioral variant frontotemporal dementia, and supranuclear vertical oculomotor palsy.

Conclusion: These clinical symptoms may reflect the distribution of tau pathologies in PSP.

Keywords: Coiled body; Frontal cortex; Globus pallidus; Midbrain tegmentum; Neurofibrillary tangle; Progressive supranuclear palsy; Subthalamic nucleus; Thread; Tufted astrocyte.