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 Scijournal_title
Annals of the New York Academy of Sciencesauthors
Ghiso J,Vidal R,Rostagno A,Miravalle L,Holton JL,Mead S,Révész T,Plant G,Frangione Bdoi
10.1111/j.1749-6632.2000.tb06908.xsubject
Has Abstractpub_date
2000-01-01 00:00:00pages
84-92eissn
0077-8923issn
1749-6632journal_volume
920pub_type
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