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

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 tri...

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Bibliographic Details
Published in:Neuropathology 2023-08, Vol.43 (4), p.326-332
Main Authors: Beck, Goichi, Yamashita, Rika, Kido, Kansuke, Ikenaka, Kensuke, Chiba, Tomoya, Yonenobu, Yuki, Saito, Yuko, Morii, Eiichi, Hasegawa, Masato, Murayama, Shigeo, Mochizuki, Hideki
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal - therapeutic use
Astrocytes
Autopsy
Basal ganglia
Basal Ganglia - pathology
Cerebellum
Cholangiocarcinoma
Dentate nucleus
Gliosis
Globus pallidus
Humans
Immunotherapy
Male
Mesencephalon
Monoclonal antibodies
monoclonal antibody
Neurofibrillary tangles
Neurofibrillary Tangles - pathology
Paralysis
Precentral gyrus
Progressive supranuclear palsy
Purkinje cells
Putamen
Substantia nigra
Supranuclear Palsy, Progressive - pathology
tau
Tau protein
tau Proteins - metabolism
Tegmentum
tilavonemab
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Summary: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.
ISSN:0919-6544
1440-1789
DOI:10.1111/neup.12890