Researchers supported by the National Institute on Aging (NIA) have discovered a novel gene, which when mutated is responsible for familial British dementia (FBD), a rare inherited disease that causes progressive dementia like that seen in patients with Alzheimer's disease (AD) and severe movement disorders. This finding provides an exciting new clue to abnormal changes in the brain that lead to dementia.
FBD, previously called familial cerebral amyloid angiopathy, was first reported in the 1940s. This autosomal dominant disorder has since been described in a large British family of more than 300 members spanning 9 generations. The most common symptoms of this devastating disease -- which usually develops in patients in their 40s and 50s -- are dementia and spasticity. A distinct feature of FBD is the development of Alzheimer's disease-like dementia instead of stroke, which is common in other inherited forms of cerebral angiopathy.
Researchers at the New York University School of Medicine in collaboration with scientists at the National Hospital for Neurology and Neurosurgery and the Institute of Neurology, both in London, England, discovered a novel gene, BRI, located on chromo-some 13. A point mutation at the stop codon of this gene results in the production of a longer-than-normal BRI precursor protein. A peptide (ABri peptide) snipped from the mutated end of the BRI precursor protein is deposited as amyloid fibrils, which are thought to contribute to neuronal dysfunction and dementia. The research is reported in the June 24, 1999, issue of Nature (Vidal, R; Frangione, B; Rostagno, A; Mead, S; Revesz, T; Plant, G and Ghiso, J "A stop-codon mutation in the BRI gene associated with familial British dementia," Nature June 24, 1999).
The research group identified the mutated gene in a female FBD family member,
who developed the disease at age 56 and died at age 65. They also found the
mutation in 7 affected FBD family members, but not in unaff
Contact: Karen Poncinki/Stephanie Clipper
NIH/National Institute on Aging