Amyloidogenesis in familial British dementia is associated with a genetic defect on chromosome 13.

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 structually unrelated to all known amyloids including A beta, the main component of the amyloid lesions in Alzheimer's disease (AD), indicating that cerebral deposition of amyloid molecules other than A beta 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.

journal_name

Ann N Y Acad Sci

authors

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

doi

10.1111/j.1749-6632.2000.tb06908.x

subject

Has Abstract

pub_date

2000-01-01 00:00:00

pages

84-92

eissn

0077-8923

issn

1749-6632

journal_volume

920

pub_type

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