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

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)285-297
Number of pages13
JournalNeurobiology of Disease
Volume11
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Cell cycle, cdc2
  • Cerebellum
  • Hyperphosphorylated tau
  • Neurodegeneration
  • Neurofibrillary tangle
  • Niemann-Pick disease type C
  • Purkinje neurons

ASJC Scopus subject areas

  • Neurology

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