Multiple System Atrophy With Predominant Striatonigral Degeneration and TAR DNA-Binding Protein of 43 kDa Pathology: An Unusual Variant of Multiple System Atrophy.
TDP‐43
multiple system atrophy
parkinsonism
α‐synuclein
Journal
Movement disorders clinical practice
ISSN: 2330-1619
Titre abrégé: Mov Disord Clin Pract
Pays: United States
ID NLM: 101630279
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
12
03
2019
revised:
24
05
2019
accepted:
13
06
2019
entrez:
21
11
2019
pubmed:
21
11
2019
medline:
21
11
2019
Statut:
epublish
Résumé
The pathological hallmark in MSA is oligodendrocytic glial cytoplasmic inclusions (GCIs) containing α-synuclein, in addition to neuronal loss and astrogliosis especially involving the striatonigral and olivopontocerebellar systems. Rarely, TAR DNA-binding protein of 43 kDa (TDP-43), a component of ubiquitinated inclusions observed mainly in amyotrophic lateral sclerosis and frontotemporal lobar degeneration has been demonstrated in cases of MSA and, more recently, was shown to colocalize with α-synuclein pathology in GCIs in 2 patients. A 66-year-old woman presented with a syndrome characterized by spasticity, dysautonomia, bulbar dysfunction, and parkinsonism. Symptoms progressed until her death at age 74. Neuropathological evaluation was performed at the New York Brain Bank at Columbia University. On gross examination, there was striking severe volume loss of the left striatum compared to mild involvement of the right striatum. Microscopically, neuronal loss and gliosis of the putamen and globus pallidus were severe on the left side, in contrast to mild involvement on the right side. Immunohistochemistry for α-synuclein revealed widespread GCIs. The sections subjected to TDP-43 antibodies showed a few GCIs with definite nucleocytoplasmic translocation of the labeling within the lenticular nucleus and within the paracentral cortex. This report adds to the evidence that TDP-43 and α-synuclein colocalize in GCIs. Whether this coexistence contributes to the pathogenesis of a subset of MSA patients or is an age-related process is not known. More cases with these peculiar pathological hallmarks might help determine whether TDP-43 contributes to neurodegeneration in a subset of patients with MSA.
Sections du résumé
BACKGROUND
BACKGROUND
The pathological hallmark in MSA is oligodendrocytic glial cytoplasmic inclusions (GCIs) containing α-synuclein, in addition to neuronal loss and astrogliosis especially involving the striatonigral and olivopontocerebellar systems. Rarely, TAR DNA-binding protein of 43 kDa (TDP-43), a component of ubiquitinated inclusions observed mainly in amyotrophic lateral sclerosis and frontotemporal lobar degeneration has been demonstrated in cases of MSA and, more recently, was shown to colocalize with α-synuclein pathology in GCIs in 2 patients.
METHODS
METHODS
A 66-year-old woman presented with a syndrome characterized by spasticity, dysautonomia, bulbar dysfunction, and parkinsonism. Symptoms progressed until her death at age 74. Neuropathological evaluation was performed at the New York Brain Bank at Columbia University.
RESULTS
RESULTS
On gross examination, there was striking severe volume loss of the left striatum compared to mild involvement of the right striatum. Microscopically, neuronal loss and gliosis of the putamen and globus pallidus were severe on the left side, in contrast to mild involvement on the right side. Immunohistochemistry for α-synuclein revealed widespread GCIs. The sections subjected to TDP-43 antibodies showed a few GCIs with definite nucleocytoplasmic translocation of the labeling within the lenticular nucleus and within the paracentral cortex.
CONCLUSIONS
CONCLUSIONS
This report adds to the evidence that TDP-43 and α-synuclein colocalize in GCIs. Whether this coexistence contributes to the pathogenesis of a subset of MSA patients or is an age-related process is not known. More cases with these peculiar pathological hallmarks might help determine whether TDP-43 contributes to neurodegeneration in a subset of patients with MSA.
Identifiants
pubmed: 31745474
doi: 10.1002/mdc3.12823
pii: MDC312823
pmc: PMC6856463
doi:
Types de publication
Journal Article
Langues
eng
Pagination
661-666Informations de copyright
© 2019 International Parkinson and Movement Disorder Society.
Déclaration de conflit d'intérêts
Columbia University Parkinson's Brain Bank is funded by the Parkinson's Foundation. The authors report no conflicts of interest.
Références
Muscle Nerve. 2007 Mar;35(3):291-302
pubmed: 17212349
Neuropathol Appl Neurobiol. 2011 Jun;37(4):358-65
pubmed: 20942898
Mov Disord. 1997 Mar;12(2):133-47
pubmed: 9087971
J Neurol. 2009 Aug;256(8):1205-14
pubmed: 19271105
Semin Neurol. 2014 Apr;34(2):210-6
pubmed: 24963680
Brain. 1994 Apr;117 ( Pt 2):235-43
pubmed: 8186951
Acta Neuropathol Commun. 2015 Jun 20;3:35
pubmed: 26091809
Acta Neuropathol. 2013 May;125(5):741-52
pubmed: 23371366
Arch Neurol. 2010 Oct;67(10):1238-50
pubmed: 20937952
Neuropathol Appl Neurobiol. 2018 Dec;44(7):707-721
pubmed: 29660838
Ann Neurol. 2015 Jun;77(6):942-52
pubmed: 25707479
Acta Neuropathol. 2008 Aug;116(2):205-13
pubmed: 18607609
Brain. 2004 Dec;127(Pt 12):2657-71
pubmed: 15509623
Acta Neuropathol. 2012 Jan;123(1):1-11
pubmed: 22101365
Science. 2006 Oct 6;314(5796):130-3
pubmed: 17023659
Mov Disord. 2017 Feb;32(2):246-255
pubmed: 28009087