TDP-43 pathology occurs infrequently in multiple system atrophy

F. Geser, J. A. Malunda, H. I. Hurtig, J. E. Duda, G. K. Wenning, S. Gilman, Phillip Anson Low, V. M Y Lee, J. Q. Trojanowski

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Aims and Methods: The α-synucleinopathy multiple system atrophy (MSA) and diseases defined by pathological 43-kDa transactive response DNA-binding protein (TDP-43) or fused in sarcoma (FUS) aggregates such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration show overlapping clinico-pathological features. Consequently, we examined MSA for evidence of TDP-43 or FUS pathology utilizing immunohistochemical studies in autopsy material from 29 MSA patients. Results: TDP-43 pathology was generally rare, and there were no FUS lesions. The TDP-43 lesions were located predominantly in medio-temporal lobe and subcortical brain areas and were comprised mainly of dystrophic processes and perivascular (and subpial) lesions. Conclusions: The multisystem clinical symptoms and signs of MSA, and in particular the neurobehavioural/cognitive and pyramidal features, appear not to result from concomitant TDP-43 or FUS pathology, but rather from widespread white matter α-synuclein positive glial cytoplasmic inclusions and neurodegeneration in keeping with a primary α-synuclein-mediated oligodendrogliopathy. The gliodegenerative disease MSA evidently results from different pathogenetic mechanisms than neurodegenerative diseases linked to pathological TDP-43.

Original languageEnglish (US)
Pages (from-to)358-365
Number of pages8
JournalNeuropathology and Applied Neurobiology
Volume37
Issue number4
DOIs
StatePublished - Jun 2011
Externally publishedYes

Fingerprint

Multiple System Atrophy
Pathology
pathology
Synucleins
lesion
Sarcoma
Neurodegenerative diseases
DNA-Binding Proteins
brain
Frontotemporal Lobar Degeneration
Brain
DNA
Inclusion Bodies
Amyotrophic Lateral Sclerosis
Temporal Lobe
protein
Neuroglia
Neurodegenerative Diseases
Signs and Symptoms
Autopsy

Keywords

  • 43-kDa transactive response DNA-binding protein
  • Multiple system atrophy

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neurology
  • Histology
  • Physiology (medical)
  • Geotechnical Engineering and Engineering Geology
  • Materials Science(all)
  • Mechanics of Materials
  • Computational Mechanics

Cite this

Geser, F., Malunda, J. A., Hurtig, H. I., Duda, J. E., Wenning, G. K., Gilman, S., ... Trojanowski, J. Q. (2011). TDP-43 pathology occurs infrequently in multiple system atrophy. Neuropathology and Applied Neurobiology, 37(4), 358-365. https://doi.org/10.1111/j.1365-2990.2010.01136.x

TDP-43 pathology occurs infrequently in multiple system atrophy. / Geser, F.; Malunda, J. A.; Hurtig, H. I.; Duda, J. E.; Wenning, G. K.; Gilman, S.; Low, Phillip Anson; Lee, V. M Y; Trojanowski, J. Q.

In: Neuropathology and Applied Neurobiology, Vol. 37, No. 4, 06.2011, p. 358-365.

Research output: Contribution to journalArticle

Geser, F, Malunda, JA, Hurtig, HI, Duda, JE, Wenning, GK, Gilman, S, Low, PA, Lee, VMY & Trojanowski, JQ 2011, 'TDP-43 pathology occurs infrequently in multiple system atrophy', Neuropathology and Applied Neurobiology, vol. 37, no. 4, pp. 358-365. https://doi.org/10.1111/j.1365-2990.2010.01136.x
Geser, F. ; Malunda, J. A. ; Hurtig, H. I. ; Duda, J. E. ; Wenning, G. K. ; Gilman, S. ; Low, Phillip Anson ; Lee, V. M Y ; Trojanowski, J. Q. / TDP-43 pathology occurs infrequently in multiple system atrophy. In: Neuropathology and Applied Neurobiology. 2011 ; Vol. 37, No. 4. pp. 358-365.
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