TDP-43-immunoreactive neuronal and glial inclusions in the neostriatum in amyotrophic lateral sclerosis with and without dementia

Zhang, Haixin; Tan, Chun-Feng; Mori, Fumiaki; Tanji, Kunikazu; Kakita, Akiyoshi; Takahashi, Hitoshi; Wakabayashi, Koichi

doi:10.1007/s00401-007-0285-7

Cited by 111Amyotrophic Lateral Sclerosis ResearchAlzheimer's disease research and treatmentsAmyloidosis: Diagnosis, Treatment, Outcomes

TDP-43-immunoreactive neuronal and glial inclusions in the neostriatum in amyotrophic lateral sclerosis with and without dementia

Zhang, Haixin, Tan, Chun-Feng, Mori, Fumiaki, Tanji, Kunikazu, Kakita, Akiyoshi, Takahashi, Hitoshi, Wakabayashi, Koichi·2007·Acta Neuropathologica

DOI 10.1007/s00401-007-0285-7

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Abstract

TDP-43 is a major component of ubiquitin-positive, tau-negative inclusions in amyotrophic lateral sclerosis (ALS), and frontotemporal lobar degeneration. We immunohistochemically examined the neostriatum from 14 cases of classic ALS (cALS), six cases of ALS with dementia (ALS-D), and 20 control subjects. TDP-43-positive, crescent or circular inclusions were found in neostriatal small neurons in 19 of 20 cases of ALS, but not in controls. Two types of inclusions were found in the large neurons: ubiquitin-positive, TDP-43-negative rod-like inclusions, and ubiquitin- and TDP-43-positive pleomorphic inclusions. The latter were specific to ALS; they were found in seven cases of cALS and in all of ALS-D. TDP-43-positive glial inclusions were also found in 12 cases of cALS and in all of ALS-D. These TDP-43-positive neuronal and glial inclusions were more numerous in ALS-D than cALS. In ALS-D, neuronal loss in the substantia nigra was found in all the cases, whereas mild gliosis without obvious neuronal loss was noted in the neostriaum in only two cases. These findings suggest that the neostriatum is also involved in the disease process of ALS with and without dementia.

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Glial TARDBP inclusions predominantly reside in oligodendrocytes.
“glial TARDBP inclusions predominantly reside in oligodendrocytes [345,346]”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [346]

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“Furthermore, glial TARDBP inclusions predominantly reside in oligodendrocytes [345,346], and expression of TARDBP in astrocytes exerts cell autonomous toxicity [299].”
Background
Sporadic amyotrophic lateral sclerosis: two pathological patterns shown by analysis of distribution of TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions
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White matter lesions in the brain with frontotemporal lobar degeneration with motor neuron disease: TDP-43-immunopositive inclusions co-localize with p62, but not ubiquitin
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Authors: Zhang, H., Tan, C.-F., Mori, F., Tanji, K., Kakita, A., Takahashi, H., & Wakabayashi, K.
Affiliations: Hirosaki University (JP)
Brain Research Institute, Niigata University (JP)
Corresponding author: Mori, Fumiaki
ORCID: Zhang, Haixin
Mori, Fumiaki
Tanji, Kunikazu
Kakita, Akiyoshi
Takahashi, Hitoshi
Wakabayashi, Koichi
Venue: Acta Neuropathologica
Publisher: Springer Science and Business Media LLC
Published: 2007-09-05
Volume: 115
Issue: 1
Pages: 115-122
ISSN: 0001-6322 (ISSN-L)
1432-0533
DOI: 10.1007/s00401-007-0285-7
OpenAlex: W2047265916
Cited by: 111
References: 46
Citations by year: 2026: 1 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 8 · 2021: 6 · 2020: 8 · 2019: 7 · 2018: 4 · 2017: 8 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 8 · 2012: 2
FWCI: 6.42
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Acta Neuropathologica (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
Keywords: TDP-43, amyotrophic lateral sclerosis, neostriatum, neuronal inclusions, glial inclusions, ubiquitin-positive inclusions, gliosis, frontotemporal lobar degeneration
MeSH terms: Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Inclusion Bodies, Dementia, DNA-Binding Proteins, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neuroglia, Neurons, Neostriatum, Ubiquitin

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TDP-43-immunoreactive neuronal and glial inclusions in the neostriatum in amyotrophic lateral sclerosis with and without dementia

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