A stop-codon mutation in the BRI gene associated with familial British dementia

Topic: Brain proteins, microglia and lab models

Familial British dementia (FBD), previously designated familial cerebral amyloid angiopathy-British type, is an autosomal dominant disorder of undetermined origin characterized by progressive dementia, spasticity, and cerebellar ataxia, with onset at around the fifth decade of life. Cerebral amyloid angiopathy, non-neuritic and perivascular plaques and neurofibrillary tangles are the predominant pathological lesions. Here we report the identification of a unique 4K protein subunit named ABri from isolated amyloid fibrils.

Key findings

• Cerebral amyloid angiopathy, non-neuritic and perivascular plaques and neurofibrillary tangles are the predominant pathological lesions.
• Here we report the identification of a unique 4K protein subunit named ABri from isolated amyloid fibrils.
• This highly insoluble peptide is a fragment of a putative type-II single-spanning transmembrane precursor that is encoded by a novel gene, BRI, located on chromosome 13.
• A single base substitution at the stop codon of this gene generates a longer open reading frame, resulting in a larger, 277-residue precursor.

Why it matters

This study identified a protein called ABri in amyloid fibrils from people with familial British dementia, a rare inherited disorder that is not Alzheimer's disease. It links a mutation in the BRI gene on chromosome 13 to this condition, but does not show how to treat, cure, or prevent Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1038/21637
• PubMed: 10391242
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{vidal1999-10391242,
  author  = {Vidal, R. and Frangione, B. and Rostagno, A. and Mead, S. and Révész, T. and Plant, G. and Ghiso, J.},
  title   = {{A stop-codon mutation in the BRI gene associated with familial British dementia}},
  journal = {Nature},
  year    = {1999},
  doi     = {10.1038/21637},
  pmid    = {10391242},
  url     = {https://doi.org/10.1038/21637}
}

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