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TDP-43 pathology occurs infrequently in multiple system atrophy.

F Geser1, J A Malunda, H I Hurtig

  • 1Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA.

Neuropathology and Applied Neurobiology
|October 15, 2010
PubMed
Summary

Multiple system atrophy (MSA) does not show TDP-43 or FUS pathology. MSA

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Area of Science:

  • Neuroscience
  • Neuropathology
  • Proteinopathies

Background:

  • Multiple system atrophy (MSA) shares clinical and pathological features with TDP-43 and FUS proteinopathies.
  • Investigating TDP-43 and FUS pathology in MSA is crucial for understanding disease mechanisms.

Purpose of the Study:

  • To examine autopsy-derived brain tissue from 29 MSA patients for evidence of TDP-43 or FUS pathology.
  • To differentiate the pathogenetic mechanisms of MSA from TDP-43 and FUS-linked neurodegenerative diseases.

Main Methods:

  • Immunohistochemical studies were performed on autopsy material from 29 MSA patients.
  • Analysis focused on the presence and distribution of TDP-43 and FUS pathology.

Main Results:

  • TDP-43 pathology was rare in MSA cases.
  • No fused in sarcoma (FUS) lesions were detected.
  • Observed TDP-43 lesions were primarily dystrophic, perivascular, and subpial, located in the medio-temporal lobe and subcortical areas.

Conclusions:

  • The clinical manifestations of MSA, including neurobehavioral, cognitive, and pyramidal signs, are not attributed to TDP-43 or FUS pathology.
  • MSA appears to be primarily an α-synuclein-mediated oligodendrogliopathy, characterized by glial cytoplasmic inclusions and neurodegeneration.
  • The pathogenesis of MSA differs from that of neurodegenerative diseases associated with pathological TDP-43.