TY - JOUR
T1 - Intranuclear neuronal inclusions in Huntington's disease and dentatorubral and pallidoluysian atrophy
T2 - Correlation between the density of inclusions and IT15 CAG triplet repeat length
AU - Becher, Mark W.
AU - Kotzuk, Joyce A.
AU - Sharp, Alan H.
AU - Davies, Stephen W.
AU - Bates, Gillian P.
AU - Price, Donald L.
AU - Ross, Christopher A.
N1 - Funding Information:
We thank the patients and families of the Baltimore Huntington’s Disease Center for their support and generosity. This research was supported by NIH NS16375, NS 34172, the Hereditary Disease Foundation; including the Lieberman Award to G.P.B., and the Huntington’s Disease Society of America.
PY - 1998/1
Y1 - 1998/1
N2 - Huntington's disease (HD) is caused by CAG triplet repeat expansion in IT15 which leads to polyglutamine stretches in the HD protein product, huntingtin. The pathological hallmark of HD is the degeneration of subsets of neurons, primarily those in the striatum and neocortex. Specific morphological markers of affected cells have not been identified in patients with HD, although a unique intranuclear inclusion was recently reported in neurons of transgenic animals expressing a construct encoding the N-terminal part (including the glutamine repeat) of huntingtin (Davies et al., 1997). In order to understand the importance of this finding, we sought for comparable nuclear abnormalities in autopsy material from patients with HD. In all 20 HD cases examined, anti-ubiquitin and N-terminal huntingtin antibodies identified intranuclear inclusions in neurons and the frequency of these lesions correlated with the length of the CAG repeat in IT15. In addition, examination of material from the related HD-like triplet repeat disorder, dentatorubral and pallidoluysian atrophy, also revealed intranuclear neuronal inclusions. These findings suggest that intranuclear inclusions containing protein aggregates may be a common feature of the pathogenesis of glutamine repeat neurodegenerative disorders.
AB - Huntington's disease (HD) is caused by CAG triplet repeat expansion in IT15 which leads to polyglutamine stretches in the HD protein product, huntingtin. The pathological hallmark of HD is the degeneration of subsets of neurons, primarily those in the striatum and neocortex. Specific morphological markers of affected cells have not been identified in patients with HD, although a unique intranuclear inclusion was recently reported in neurons of transgenic animals expressing a construct encoding the N-terminal part (including the glutamine repeat) of huntingtin (Davies et al., 1997). In order to understand the importance of this finding, we sought for comparable nuclear abnormalities in autopsy material from patients with HD. In all 20 HD cases examined, anti-ubiquitin and N-terminal huntingtin antibodies identified intranuclear inclusions in neurons and the frequency of these lesions correlated with the length of the CAG repeat in IT15. In addition, examination of material from the related HD-like triplet repeat disorder, dentatorubral and pallidoluysian atrophy, also revealed intranuclear neuronal inclusions. These findings suggest that intranuclear inclusions containing protein aggregates may be a common feature of the pathogenesis of glutamine repeat neurodegenerative disorders.
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U2 - 10.1006/nbdi.1998.0168
DO - 10.1006/nbdi.1998.0168
M3 - Article
C2 - 9666478
AN - SCOPUS:0031918640
SN - 0969-9961
VL - 4
SP - 387
EP - 397
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 6
ER -