Corticobasal degeneration with olivopontocerebellar atrophy and TDP-43 pathology: an unusual clinicopathologic variant of CBD.
Corticobasal degeneration (CBD) is a disorder affecting cognition and movement due to a progressive neurodegeneration associated with distinctive neuropathologic features, including abnormal phosphorylated tau protein in neurons and glia in cortex, basal ganglia, diencephalon, and brainstem, as well as ballooned neurons and astrocytic plaques. We identified three cases of CBD with olivopontocerebellar atrophy (CBD-OPCA) that did not have α-synuclein-positive glial cytoplasmic inclusions of multiple system atrophy (MSA). Two patients had clinical features suggestive of progressive supranuclear palsy (PSP), and the third case had cerebellar ataxia thought to be due to idiopathic OPCA. Neuropathologic features of CBD-OPCA are compared to typical CBD, as well as MSA and PSP. CBD-OPCA and MSA had marked neuronal loss in pontine nuclei, inferior olivary nucleus, and Purkinje cell layer. Neuronal loss and grumose degeneration in the cerebellar dentate nucleus were comparable in CBD-OPCA and PSP. Image analysis of tau pathology showed greater infratentorial tau burden, especially in pontine base, in CBD-OPCA compared with typical CBD. In addition, CBD-OPCA had TDP-43 immunoreactive neuronal and glial cytoplasmic inclusions and threads throughout the basal ganglia and in olivopontocerebellar system. CBD-OPCA met neuropathologic research diagnostic criteria for CBD and shared tau biochemical characteristics with typical CBD. These results suggest that CBD-OPCA is a distinct clinicopathologic variant of CBD with olivopontocerebellar TDP-43 pathology.
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA. kouri.naomi@mayo.edu
Naomi
N
Kouri
Kenichi
K
Oshima
Makio
M
Takahashi
Melissa E
ME
Murray
Zeshan
Z
Ahmed
Joseph E
JE
Parisi
Shu-Hui C
SH
Yen
Dennis W
DW
Dickson
D000368:Aged; D002524:Cerebellar Ataxia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009849:Olivopontocerebellar Atrophies / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D013494:Supranuclear Palsy, Progressive / Q000209:etiology / Q000378:metabolism / Q000473:pathology
D004268:DNA-Binding Proteins