Patients lacking the major CNS myelin protein, proteolipid protein 1, develop length-dependent axonal degeneration in the absence of demyelination and inflammation

• DOI: 10.1093/brain/awf043
• Publication Date: 2002-07-26T22:48:15Z
• Authors: J. Y. Garbern; D. A. Yool; G. J. Moore; I. B. Wilds; M. W. Faulk; M. Klugmann; K.-A. Nave; E. A. Sistermans; M. S. van der Knaap; T. D. Bird; M. E. Shy; J. A. Kamholz; I. R. Griffiths
• Keywords: Proteolipid protein 1; Degeneration (medical); Axonal Degeneration

Axonal degeneration contributes to clinical disability in the acquired demyelinating disease multiple sclerosis. occurs during acute attacks, associated with inflammation, and chronic progressive phase of which inflammation is not prominent. To explore importance interactions between oligodendrocytes axons CNS, we analysed brains rodents humans a null mutation gene encoding major CNS myelin protein, proteolipid protein (PLP1, previously PLP). Histological analyses Plp1 mice autopsy material from patients PLP1 mutations were performed evaluate axonal integrity. In vivo proton magnetic resonance spectroscopy (MRS) was conducted measure levels N‐acetyl aspartate (NAA), marker Length‐dependent without demyelination identified mice. Proton MRS PLP1‐deficient showed reduced NAA levels, consistent loss. Analysis patients’ brain tissue also demonstrated length‐dependent pattern loss significant demyelination. Therefore, as well lacking PLP1. This length‐dependent, similar that found PNS inherited neuropathy, CMT1A, but Disruption PLP1‐mediated axonal–glial thus probably causes this degeneration. A mechanism may be responsible for occur