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Amyloidogenesis in familial British dementia is associated with a genetic defect on chromosome 13

J Ghiso1, R Vidal, A Rostagno

  • 1Department of Pathology, New York University School of Medicine, 550 First Avenue, Room TH-432, New York, NY 10016, USA. ghisoj01@popmail.med.nyu.edu

Annals of the New York Academy of Sciences
|February 24, 2001
PubMed

Insights

Familial British dementia (FBD) involves amyloid deposits and neurofibrillary tangles. A unique amyloid subunit (ABri), unrelated to Alzheimer's disease A beta, causes FBD by triggering neurodegeneration.

Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • Familial British dementia (FBD) is characterized by cerebral amyloid deposits and neurofibrillary tangles.
  • The amyloid subunit in FBD, ABri, originates from the BRI gene on chromosome 13.

Purpose of the Study:

  • To investigate the molecular basis of ABri formation in FBD.
  • To understand the role of ABri in FBD pathogenesis and its distinction from Alzheimer's disease.

Main Methods:

  • Genetic analysis of the BRI gene in FBD patients.
  • Biochemical characterization of the ABri precursor protein (ABriPP-277).
  • Study of ABri processing and aggregation.

Main Results:

  • A single base substitution in the BRI gene generates an elongated precursor, ABriPP-277.
  • Proteolytic processing yields the 34-amino acid ABri, which rapidly aggregates.
  • ABri is structurally distinct from the A beta amyloid found in Alzheimer's disease.

Conclusions:

  • Amyloid deposition, even by non-A beta molecules like ABri, can initiate neurodegeneration and dementia.
  • Vascular and parenchymal amyloid deposition is crucial for neurodegeneration in FBD.
  • FBD provides insight into the primary role of amyloid in initiating neurodegenerative processes.

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