Globular Glial Mixed Four Repeat Tau and TDP-43 Proteinopathy with Motor Neuron Disease and Frontotemporal Dementia.

Brain Pathology
Ryoko TakeuchiHitoshi Takahashi

Abstract

Amyotrophic lateral sclerosis (ALS) may be accompanied by frontotemporal dementia (FTD). We report a case of glial mixed tau and TDP-43 proteinopathies in a Japanese patient diagnosed clinically as having ALS-D. Autopsy revealed loss of lower motor neurons and degeneration of the pyramidal tracts in the spinal cord and brain stem. The brain showed frontotemporal lobar degeneration (FTLD), the most severe neuronal loss and gliosis being evident in the precentral gyrus. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. AT8 immunostaining revealed that predominant occurrence of astrocytic tau lesions termed globular astrocytic inclusions (GAIs) was a feature of the affected regions. These GAIs were Gallyas-Braak negative. Neuronal and oligodendrocytic tau lesions were comparatively scarce. pS409/410 immunostaining also revealed similar neuronal and glial TDP-43 lesions. Interestingly, occasional co-localization of tau and TDP-43 was evident in the GAIs. Immunoblot analyses revealed band patterns characteristic of a 4-repeat (4R) tauopathy, corticobasal degeneration and a TDP-43 proteinopathy, ALS/FTLD-TDP Type B. No mutations were found in the MAPT or TD...Continue Reading

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Citations

Feb 7, 2019·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Tomoya KonKoichi Wakabayashi
May 28, 2019·Journal of Neuropathology and Experimental Neurology·Claire H StevensLezanne Ooi
Sep 5, 2020·Acta Neuropathologica Communications·Vera I WiersmaWiep Scheper
Dec 18, 2020·Frontiers in Neurology·Michael J StrongKathryn Volkening
Jan 20, 2021·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Mitsuaki HiranoNorio Ozaki
Mar 18, 2021·Neuropathology and Applied Neurobiology·Ellen GelpiIsidre Ferrer
Nov 11, 2021·Molecular Neurobiology·Tiziana PetrozzielloGhazaleh Sadri-Vakili

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