An autopsy case of progressive supranuclear palsy treated with monoclonal antibody against tau

Author:

Beck Goichi1ORCID,Yamashita Rika1,Kido Kansuke2,Ikenaka Kensuke1,Chiba Tomoya1,Yonenobu Yuki1ORCID,Saito Yuko3,Morii Eiichi2,Hasegawa Masato4ORCID,Murayama Shigeo135ORCID,Mochizuki Hideki1ORCID

Affiliation:

1. Department of Neurology Osaka University Graduate School of Medicine Suita Japan

2. Department of Pathology Osaka University Graduate School of Medicine Suita Japan

3. Department of Neurology and Neuropathology (Brain Bank for Aging Research) Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Tokyo Japan

4. Dementia Research Project Tokyo Metropolitan Institute of Medical Science Tokyo Japan

5. Brain Bank for Neurodevelopmental, Neurological and Psychiatric Disorders, Molecular Research Center for Children's Mental Development, United Graduate School of Child Development Osaka University Suita Japan

Abstract

We report an autopsy case of progressive supranuclear palsy (PSP‐Richardson syndrome). The individual had been enrolled in a phase 2 trial and received a monoclonal tau antibody (tilavonemab, ABBV‐8E12); he died of intrahepatic cholangiocarcinoma and gastrointestinal bleeding during the clinical trial. Neuropathological examination demonstrated neuronal loss, gliosis, and widespread deposits of phosphorylated tau in the neurofibrillary tangles, tufted astrocytes, coiled bodies, and threads, which mainly occurred in the inferior olive nucleus, dentate nucleus of the cerebellum, substantia nigra, midbrain tegmentum, subthalamic nuclei, globus pallidus, putamen, and precentral gyrus, confirming typical PSP pathology. Phosphorylated tau was also found to accumulate in Betz cells, Purkinje cells, and pencil fibers in the basal ganglia. In conclusion, no additional changes or pathological modifications, which were expected from immunotherapy targeting tau, were visible in the present case.

Funder

Japan Agency for Medical Research and Development

Publisher

Wiley

Subject

Neurology (clinical),General Medicine,Pathology and Forensic Medicine

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