23 June 1999. In tomorrow's issue of Nature, Jorge Ghiso and
colleagues at New York University, and coworkers at the National
Hospital for Neurology and Neurosurgery in London, report that they have
found the gene mutation that produces the amyloid in Familial British
Dementia (FBD). Previously called familial cerebral amyloid
angiopathy-British type, FBD is an autosomal dominant disorder that
shares features of Alzheimer's disease, including amyloid deposits,
neurofibrillary tangles, neuronal loss, and progressive dementia. It is
distinguished from Alzheimer's by plaque deposition in the cerebellum
and accompanying cerebellar ataxia. It is only known to exist in
38 descendants of a British woman who died in 1883.
The researchers isolated a 4K protein from amyloid plaques recovered
from autopsy tissue of a woman who developed the disease at age 56 and
died at age 65. They named the highly insoluble peptide ABri and
determined that it is part of a pututive type-II transmembrane precursor
encoded by a gene which they named BRI, on chromosome 13. In family
members with FBD, the BRI gene lacks a stop codon, the result being that
the precursor protein winds up with 277 instead of 266 amino acids. The
amyloid protein deposited in the brains of patients with FBD consists of
the 34 carboxy-terminal amino acids from this larger mutant protein.-Hakon Heimer.
Reference:Vidal R, Frangione B, Rostagno A, Mead S, Revesz T, Plant G, Ghiso J. A stop-codon mutation in the BRI gene associated with familial British dementia.
Nature 1999 Jun 24;399(6738):776-81. Abstract