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, P. A. Low, V. M.Y. Lee, J. Q. Trojanowski

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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
Issue number4
StatePublished - Jun 2011


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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Neurology
  • Clinical Neurology
  • Physiology (medical)


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