C9ORF72 expansions, parkinsonism, and Parkinson disease: a clinicopathologic study.
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ABSTRACT: Objective
To determine the histopathologic bases for the observed incidence of parkinsonism in families with C9ORF72 expansions, which typically cause amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia.Methods
DNA was extracted from 377 brains with the histopathologic diagnosis of idiopathic Parkinson disease or related disorders and analyzed for C9ORF72 expansions. ?-Synuclein and p62 immunohistochemistry of the substantia nigra (SN) was undertaken in brains of 17 ALS cases with (C9ORF72+) and 51 without (C9ORF72-) the C9ORF72 expansion.Results
Only 1 of 338 cases with pathologically confirmed idiopathic Parkinson disease had a C9ORF72 expansion. Similarly, only 1 of 17 C9ORF72+ brains displayed features suggestive of ?-synucleinopathy. In contrast, p62-positive, TDP-43-negative neuronal cytoplasmic inclusions within the SN were considerably more frequent in C9ORF72+ brain tissue than in the C9ORF72- brains (p = 0.005). Furthermore, there was a more marked loss of dopaminergic neurons in the SN of C9ORF72+ ALS brains than C9ORF72- ALS brains (p = 0.029).Conclusions
SN involvement is common in C9ORF72+ ALS but can be clearly distinguished from Parkinson disease-related mechanisms by the presence of p62-positive inclusions and the absence of ?-synuclein-positive Lewy bodies or Lewy neurites.
SUBMITTER: Cooper-Knock J
PROVIDER: S-EPMC3908460 | biostudies-literature | 2013 Aug
REPOSITORIES: biostudies-literature
Publications
C9ORF72 expansions, parkinsonism, and Parkinson disease: a clinicopathologic study.
Cooper-Knock Johnathan J Frolov Antonina A Highley J Robin JR Charlesworth Gavin G Kirby Janine J Milano Antonio A Hartley Judith J Ince Paul G PG McDermott Christopher J CJ Lashley Tammaryn T Revesz Tamas T Shaw Pamela J PJ Wood Nicholas W NW Bandmann Oliver O
Neurology 20130724 9
<h4>Objective</h4>To determine the histopathologic bases for the observed incidence of parkinsonism in families with C9ORF72 expansions, which typically cause amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia.<h4>Methods</h4>DNA was extracted from 377 brains with the histopathologic diagnosis of idiopathic Parkinson disease or related disorders and analyzed for C9ORF72 expansions. α-Synuclein and p62 immunohistochemistry of the substantia nigra (SN) was undertaken in brains of 1 ...[more]
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