Vaccination with amyloid-β peptide induces autoimmune encephalomyelitis in C57/BL6 mice

Roberto Furlan, Elena Brambilla, Francesca Sanvito, Luca Roccatagliata, Stefano Olivieri, Alessandra Bergami, Stefano Pluchino, Antonio Uccelli, Giancarlo Comi, Gianvito Martino

Research output: Contribution to journalArticle

Abstract

Recent experimental evidence shows that vaccination with amyloid-β peptide (Aβ) of transgenic mouse models of Alzheimer's disease protects from the pathological accumulation of amyloid within the CNS. Phase I/lI clinical trials of Aβ vaccination in mild to moderate Alzheimer's disease have been undertaken. Unexpectedly, one of these trials has been suspended because 15 patients showed clinical signs consistent with CNS inflammation. Here, we show that C57BL/6 mice immunized with Aβ1-42 peptide develop an inflammatory disease of the CNS characterized by the presence both in the brain and spinal cord of perivenular inflammatory foci containing macrophages, T and B cells, and immunoglobulins. The experimental disease was observed only when pertussis toxin, an agent known to favour autoimmune processes, was co-administered. The immune-mediated CNS reaction was associated to Aβ-induced CD4+ cells showing a Th1-type cytokine expression profile and to elevated levels of circulating anti-Aβ immunoglobulins. Our results indicate that vaccination with Aβ could determine, under certain circumstances, an aberrant autoimmune-type reaction to Aβ resulting in a perivenular inflammatory encephalomyelitis.

Original languageEnglish
Pages (from-to)285-291
Number of pages7
JournalBrain
Volume126
Issue number2
DOIs
Publication statusPublished - Feb 1 2003

Keywords

  • Alzheimer's disease
  • Amyloid-β peptide
  • Encephalomyelitis
  • Vaccination

ASJC Scopus subject areas

  • Neuroscience(all)

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    Furlan, R., Brambilla, E., Sanvito, F., Roccatagliata, L., Olivieri, S., Bergami, A., Pluchino, S., Uccelli, A., Comi, G., & Martino, G. (2003). Vaccination with amyloid-β peptide induces autoimmune encephalomyelitis in C57/BL6 mice. Brain, 126(2), 285-291. https://doi.org/10.1093/brain/awg031