Perry syndrome: A distinctive type of TDP-43 proteinopathy

Takayasu Mishima, Shunsuke Koga, Wen Lang Lin, Koji Kasanuki, Monica Castanedes-Casey, Zbigniew K. Wszolek, Shin J. Oh, Yoshio Tsuboi, Dennis W. Dickson

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Perry syndrome is a rare atypical parkinsonism with depression, apathy, weight loss, and central hypoventilation caused by mutations in dynactin p150glued (DCTN1). A rare distal hereditary motor neuropathy, HMN7B, also has mutations in DCTN1. Perry syndrome has TAR DNA-binding protein of 43 kDa (TDP-43) inclusions as a defining feature. Other TDP-43 proteinopathies include amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with and without motor neuron disease (FTLD-MND). TDP-43 forms aggregates in neuronal cytoplasmic inclusions (NCIs), neuronal intranuclear inclusions, dystrophic neurites (DNs), as well as axonal spheroids, oligodendroglial cytoplasmic inclusions, and perivascular astrocytic inclusions (PVIs). We performed semiquantitative assessment of these lesions and presence of dynactin subunit p50 lesions in 3 cases of Perry syndrome and one of HMN7B. We compared them with 3 cases of FTLD-MND, 3 of ALS, and 3 of hippocampal sclerosis (HpScl). Perry syndrome had NCIs, DNs, and frequent PVIs and spheroids. Perry syndrome cases were similar, but different from ALS, FTLD-MND, and HpScl. TDP-43 pathology was not detected in HMN7B. Dynactin p50 inclusions were observed in both Perry syndrome and HMN7B, but not in the other conditions. These results suggest that Perry syndrome may be distinctive type of TDP-43 proteinopathy.

Original languageEnglish (US)
Pages (from-to)676-682
Number of pages7
JournalJournal of Neuropathology and Experimental Neurology
Volume76
Issue number8
DOIs
StatePublished - 2017

Keywords

  • Amyotrophic lateral sclerosis
  • DCTN1
  • Distal hereditary motor neuropathy 7B
  • Frontotemporal lobar degeneration with motor neuron disease
  • Perivascular astrocytic inclusions
  • Perry syndrome
  • TDP-43

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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    Mishima, T., Koga, S., Lin, W. L., Kasanuki, K., Castanedes-Casey, M., Wszolek, Z. K., Oh, S. J., Tsuboi, Y., & Dickson, D. W. (2017). Perry syndrome: A distinctive type of TDP-43 proteinopathy. Journal of Neuropathology and Experimental Neurology, 76(8), 676-682. https://doi.org/10.1093/jnen/nlx049