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
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