A newly formed amyloidogenic fragment due to a stop codon mutation causes familial British dementia

J. Ghiso, Ruben Vidal, A. Rostagno, S. Mead, T. Révész, G. Plant, B. Frangione

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Familial British dementia (FBD) is an early-onset autosomal dominant disorder characterized by progressive cognitive impairment, spasticity, and cerebellar ataxia. Hippocampal neurofibrillar degeneration and widespread parenchymal and vascular amyloid deposits are the main neuropathological lesions. Amyloid fibrils are composed of a novel 34 amino acid subunit (ABri) with no sequence identity to any known amyloid molecule. The peptide derives from a larger precursor protein codified by a single gene BRI on chromosome 13. Affected family members have a single base substitution at the stop codon of the BRI gene that generates a longer open-reading frame resulting in a larger precursor protein. The release of the 34 C-terminal amino acids from the mutated precursor originates the ABri amyloid subunit. Our discovery of a new amyloid associated with the development of dementia supports the concept that amyloid peptides may be of primary importance in the initiation of neurodegeneration.

Original languageEnglish (US)
Pages (from-to)129-137
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume903
StatePublished - 2000
Externally publishedYes

Fingerprint

Terminator Codon
Amyloid
Abrus
Mutation
Protein Precursors
Amino Acids
Chromosomes, Human, Pair 13
Genes
Cerebellar Ataxia
Peptides
Amyloid Plaques
Open Reading Frames
Blood Vessels
Dementia
Chromosomes
Familial British Dementia
Familial
Causes
Precursor
Substitution reactions

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ghiso, J., Vidal, R., Rostagno, A., Mead, S., Révész, T., Plant, G., & Frangione, B. (2000). A newly formed amyloidogenic fragment due to a stop codon mutation causes familial British dementia. Annals of the New York Academy of Sciences, 903, 129-137.

A newly formed amyloidogenic fragment due to a stop codon mutation causes familial British dementia. / Ghiso, J.; Vidal, Ruben; Rostagno, A.; Mead, S.; Révész, T.; Plant, G.; Frangione, B.

In: Annals of the New York Academy of Sciences, Vol. 903, 2000, p. 129-137.

Research output: Contribution to journalArticle

Ghiso, J, Vidal, R, Rostagno, A, Mead, S, Révész, T, Plant, G & Frangione, B 2000, 'A newly formed amyloidogenic fragment due to a stop codon mutation causes familial British dementia', Annals of the New York Academy of Sciences, vol. 903, pp. 129-137.
Ghiso, J. ; Vidal, Ruben ; Rostagno, A. ; Mead, S. ; Révész, T. ; Plant, G. ; Frangione, B. / A newly formed amyloidogenic fragment due to a stop codon mutation causes familial British dementia. In: Annals of the New York Academy of Sciences. 2000 ; Vol. 903. pp. 129-137.
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