Niemann-Pick Disease Type C Yields Possible Clue for Why Cerebellar Neurons Do Not Form Neurofibrillary Tangles

Bitao Bu; Hans Klunemann; Kinuko Suzuki; Jin Li; Thomas Bird; Lee-Way Jin; Inez Vincent

Neurobiology of Disease (Nov 2002)

Niemann-Pick Disease Type C Yields Possible Clue for Why Cerebellar Neurons Do Not Form Neurofibrillary Tangles

Bitao Bu,
Hans Klunemann,
Kinuko Suzuki,
Jin Li,
Thomas Bird,
Lee-Way Jin,
Inez Vincent

Affiliations

Bitao Bu: Department of Pathology, University of Washington, Box 357705, Seattle, Washington, 98195; Department of Neurology, University of Washington, Box 357705, Seattle, Washington, 98195; Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Peoples Republic of China; University of Regensburg, 93053, Regensburg, Germany; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, 27599
Hans Klunemann: Department of Pathology, University of Washington, Box 357705, Seattle, Washington, 98195; Department of Neurology, University of Washington, Box 357705, Seattle, Washington, 98195; Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Peoples Republic of China; University of Regensburg, 93053, Regensburg, Germany; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, 27599
Kinuko Suzuki: Department of Pathology, University of Washington, Box 357705, Seattle, Washington, 98195; Department of Neurology, University of Washington, Box 357705, Seattle, Washington, 98195; Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Peoples Republic of China; University of Regensburg, 93053, Regensburg, Germany; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, 27599
Jin Li: Department of Pathology, University of Washington, Box 357705, Seattle, Washington, 98195; Department of Neurology, University of Washington, Box 357705, Seattle, Washington, 98195; Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Peoples Republic of China; University of Regensburg, 93053, Regensburg, Germany; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, 27599
Thomas Bird: Department of Pathology, University of Washington, Box 357705, Seattle, Washington, 98195; Department of Neurology, University of Washington, Box 357705, Seattle, Washington, 98195; Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Peoples Republic of China; University of Regensburg, 93053, Regensburg, Germany; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, 27599
Lee-Way Jin: Department of Pathology, University of Washington, Box 357705, Seattle, Washington, 98195; Department of Neurology, University of Washington, Box 357705, Seattle, Washington, 98195; Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Peoples Republic of China; University of Regensburg, 93053, Regensburg, Germany; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, 27599
Inez Vincent: Department of Pathology, University of Washington, Box 357705, Seattle, Washington, 98195; Department of Neurology, University of Washington, Box 357705, Seattle, Washington, 98195; Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Peoples Republic of China; University of Regensburg, 93053, Regensburg, Germany; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, 27599

Journal volume & issue: Vol. 11, no. 2
pp. 285 – 297

Abstract

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It is unknown why cerebellar neurons resist neurofibrillary tangle (NFT) formation. In Niemann-Pick disease Type C (NPC), NFT-mediated neurodegeneration occurs throughout brain, but the cerebellum degenerates conspicuously without NFT. To understand why, we have studied markers of NFT pathogenesis in cerebellum from 17 NPC cases, all having abundant NFT in forebrain. Remarkably, we found that NPC cerebella display several early markers of NFT formation, i.e., hyperphosphorylated tau and an array of cell cycle regulators, suggesting that cerebellar neurons in NPC undergo similar modifications as other neurons that develop NFT. However, cerebellar neurons are deficient in tau, the building block of NFT, and this may be one reason for their inability to form NFT. Even without NFT, cerebellar neurodegeneration may be triggered by the inappropriate activation of the cell cycle cdc2 kinase, and the npc-1 murine model provides an opportunity to test this hypothesis.

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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