Amyloidogenesis in Familial British dementia is associated with a genetics defect on chromosome 13

J. Ghiso, R. Vidal, A. Rostagno, L. Miravalle, J. L. Holton, S. Mead, T. Révész, G. Plant, B. Frangione

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Familial British dementia (FBD) is a disorder characterized by the presence of amyloid deposits in cerebral blood vessels and brain parenchyma coexisting with neurofibrillary tangles in limbic areas. The amyloid subunit (ABri) is a 4 kDa fragment of a 266 amino acid type II single-spanning transmembrane precursor protein encoded by the BRI gene located on chromosome 13. In FBD patients, a single base substitution at the stop codon of this gene generates a larger 277-residue precursor (ABriPP-277). Proteolytic processing by a furin-like enzyme at the C-terminus of the elongated precursor generates the 34 amino acid ABri that undergoes rapid aggregation and fibrillization. ABri is structurally unrelated to all known amyloids including Aβ, the main component of the amyloid lesions in Alzheimer's disease (AD), indicating that cerebral deposition of amyloid molecules other than Aβ can trigger similar neuropathological changes leading to neuronal loss and dementia. These data support the concept that amyloid deposition in the vascular wall and brain parenchyma is of primary importance in the initiation of neurogeneration.

Original languageEnglish (US)
Pages (from-to)84-92
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume920
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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