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Findings About Other Dementias Provide Clues to Alzheimer's Disease

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By 1999 Progress Report by the NIA/NIH • • December 13, 1999

Scientists supported by NIA have discovered a novel gene, which when mutated, is responsible for familial British dementia (FBD), a rare inherited disease that causes severe movement disorders and progressive dementia similar to that seen in AD.

FBD was first reported in the 1940s, but until now, the identity of the major component of the amyloid deposits seen in the disease remained unknown. In this study, a research team at the New York University School of Medicine and the National Hospital for Neurology and Neurosurgery and the Institute of Neurology, both in London, conducted a detailed biochemical analysis of the amyloid fibrils found in the FBD plaques (Vidal et al., 1999). The researchers found a unique peptide (a protein fragment) named ABri and from the sequence of this protein fragment they were able to identify the gene, BRI, which is located on chromosome 13. A mutation at a particular point along this gene results in the production of a longer-than-normal Bri protein. The ABri peptide, which is snipped from the mutated end of the Bri protein is deposited as amyloid fibrils. These plaques are thought to lead to the neuronal dysfunction and dementia that
characterizes FBD.

The discovery of this FBD gene and the insights into how its mutation leads to amyloid deposition opens another important window for understanding AD and dementias that occur in other neurological disorders. A better understanding of movement disorders, which are common in older people, also may emerge when the ways in which the ABri amyloid causes the disease are more fully elucidated in further studies.

Source: National Institutes of Health; National Institute on Aging

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