Journal article
Pallidonigral TDP-43 pathology in Perry syndrome
Parkinsonism & related disorders, Vol.15(4), pp.281-286
2009
DOI: 10.1016/j.parkreldis.2008.07.005
PMCID: PMC2693935
PMID: 18723384
Abstract
Autosomal dominant parkinsonism, hypoventilation, depression and severe weight loss (Perry syndrome) is an early-onset rapidly progressive disease. At autopsy, previous studies have found severe neuronal loss in the substantia nigra without Lewy bodies. Transactive response DNA-binding protein of 43
kDa (TDP-43) has recently been identified as a major ubiquitinated constituent of neuronal and glial inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions and in amyotrophic lateral sclerosis. This study reports clinical, genetic and neuropathologic investigations of Perry syndrome.
Clinical data and autopsy brain tissue samples were collected from eight patients from four genealogically unrelated kindreds with Perry syndrome. Brain tissue was studied with immunohistochemistry and biochemistry for TDP-43. Patients were screened for mutations in the
progranulin (
GRN) and
TDP-43 (
TARDBP) genes.
The mean age at onset was 47
years (range 40–56), and the mean age at death was 52
years (range 44–64). In all patients, we identified TDP-43-positive neuronal inclusions, dystrophic neurites and axonal spheroids in a predominantly pallidonigral distribution, and we demonstrated changes in solubility and electrophoretic mobility of TDP-43 in brain tissue. The inclusions were highly pleomorphic and predominated in the extrapyramidal system, sparing the cortex, hippocampus and motor neurons. There were no mutations in
GRN or
TARDBP.
Perry syndrome displays unique TDP-43 pathology that is selective for the extrapyramidal system and spares the neocortex and motor neurons.
Details
- Title: Subtitle
- Pallidonigral TDP-43 pathology in Perry syndrome
- Creators
- Christian Wider - Department of Neurology, Mayo Clinic, Jacksonville, FL, USADennis W Dickson - Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USAA. Jon Stoessl - Department of Neurology, Pacific Parkinson's Research Centre, Vancouver, BC, CanadaYoshio Tsuboi - Department of Neurology, Fukuoka University, Fukuoka, JapanFrançoise Chapon - Laboratory of Pathology, CHU-Caen, Caen, FranceLudwig Gutmann - Department of Neurology, West Virginia University, Morgantown, WV, USABernard Lechevalier - Laboratory of Pathology, CHU-Caen, Caen, FranceDonald B Calne - Department of Neurology, Pacific Parkinson's Research Centre, Vancouver, BC, CanadaDavid A Personett - Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USAMary Hulihan - Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USAJennifer Kachergus - Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USARosa Rademakers - Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USAMatthew C Baker - Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USALinda L Grantier - Department of Neurology, Pacific Parkinson's Research Centre, Vancouver, BC, CanadaO.K Sujith - Department of Neurology, Pacific Parkinson's Research Centre, Vancouver, BC, CanadaLaura Brown - Department of Neurology, Mayo Clinic, Jacksonville, FL, USASusan Calne - Department of Neurology, Pacific Parkinson's Research Centre, Vancouver, BC, CanadaMatthew J Farrer - Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USAZbigniew K Wszolek - Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
- Resource Type
- Journal article
- Publication Details
- Parkinsonism & related disorders, Vol.15(4), pp.281-286
- DOI
- 10.1016/j.parkreldis.2008.07.005
- PMID
- 18723384
- PMCID
- PMC2693935
- NLM abbreviation
- Parkinsonism Relat Disord
- ISSN
- 1353-8020
- eISSN
- 1873-5126
- Publisher
- Elsevier Ltd
- Language
- English
- Date published
- 2009
- Academic Unit
- Neurology
- Record Identifier
- 9984014019102771
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