Intranuclear Neuronal Inclusions in Huntington's Disease and Dentatorubral and Pallidoluysian Atrophy: Correlation between the Density of Inclusions andIT15CAG Triplet Repeat Length

Mark W. Becher; Joyce A. Kotzuk; Alan H. Sharp; Stephen W. Davies; Gillian P. Bates; Donald L. Price; Christopher A. Ross

Neurobiology of Disease (Jan 1998)

Intranuclear Neuronal Inclusions in Huntington's Disease and Dentatorubral and Pallidoluysian Atrophy: Correlation between the Density of Inclusions andIT15CAG Triplet Repeat Length

Mark W. Becher,
Joyce A. Kotzuk,
Alan H. Sharp,
Stephen W. Davies,
Gillian P. Bates,
Donald L. Price,
Christopher A. Ross

Affiliations

Mark W. Becher: Department of Pathology, Division of Neuropathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Department of Anatomy and Developmental Biology, University College London, London, WC1E 6BT, United Kingdom; Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, SE1 9RT, United Kingdom
Joyce A. Kotzuk: Department of Pathology, Division of Neuropathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Department of Anatomy and Developmental Biology, University College London, London, WC1E 6BT, United Kingdom; Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, SE1 9RT, United Kingdom
Alan H. Sharp: Department of Pathology, Division of Neuropathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Department of Anatomy and Developmental Biology, University College London, London, WC1E 6BT, United Kingdom; Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, SE1 9RT, United Kingdom
Stephen W. Davies: Department of Pathology, Division of Neuropathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Department of Anatomy and Developmental Biology, University College London, London, WC1E 6BT, United Kingdom; Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, SE1 9RT, United Kingdom
Gillian P. Bates: Department of Pathology, Division of Neuropathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Department of Anatomy and Developmental Biology, University College London, London, WC1E 6BT, United Kingdom; Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, SE1 9RT, United Kingdom
Donald L. Price: Department of Pathology, Division of Neuropathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Department of Anatomy and Developmental Biology, University College London, London, WC1E 6BT, United Kingdom; Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, SE1 9RT, United Kingdom
Christopher A. Ross: Department of Pathology, Division of Neuropathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Division of Neuropathology, Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2196; Department of Anatomy and Developmental Biology, University College London, London, WC1E 6BT, United Kingdom; Division of Medical and Molecular Genetics, UMDS, Guy's Hospital, London, SE1 9RT, United Kingdom

Journal volume & issue: Vol. 4, no. 6
pp. 387 – 397

Abstract

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Huntington's disease (HD) is caused by CAG triplet repeat expansion inIT15which 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 (Davieset 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 inIT15. 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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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