Chromosome 13 dementia syndromes as models of neurodegeneration

Amyloid. 2001 Dec;8(4):277-84. doi: 10.3109/13506120108993826.

Abstract

Two hereditary conditions, familial British dementia (FBD) and familial Danish dementia (FDD), are associated with amyloid deposition in the central nervous system and neurodegeneration. The two amyloid proteins, ABri and ADan, are degradation products of the same precursor molecule BriPP bearing different genetic defects, namely a Stop-to-Arg mutation in FBD and a ten-nucleotide duplication-insertion immediately before the stop codon in FDD. Both de novo created amyloid peptides have the same length (34 amino acids) and the same post-translational modification (pyroglutamate) at their N-terminus. Neurofibrillary tangles containing the classical paired helical filaments as well as neuritic components in many instances co-localize with the amyloid deposits. In both disorders, the pattern of hyperphosphorylated tau immunoreactivity is almost indistinguishable from that seen in Alzheimer's disease. These issues argue for the primary importance of the amyloid deposits in the mechanism(s) of neuronal cell loss. We propose FBD and FDD, the chromosome 13 dementia syndromes, as models to study the molecular basis of neurofibrillary degeneration, cell death and amyloid formation in the brain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Amyloid / genetics
  • Amyloid / metabolism
  • Chromosomes, Human, Pair 13 / genetics*
  • Dementia / genetics*
  • Dementia / metabolism
  • Dementia / pathology
  • Denmark
  • Heredodegenerative Disorders, Nervous System / genetics*
  • Heredodegenerative Disorders, Nervous System / metabolism
  • Heredodegenerative Disorders, Nervous System / pathology
  • Humans
  • Models, Genetic
  • Models, Neurological
  • Molecular Sequence Data
  • Mutation
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology
  • Syndrome
  • United Kingdom

Substances

  • Amyloid