Modeling familial British and Danish dementia

Brain Struct Funct. 2010 Mar;214(2-3):235-44. doi: 10.1007/s00429-009-0221-9. Epub 2009 Sep 25.

Abstract

Familial British dementia (FBD) and familial Danish dementia (FDD) are two autosomal dominant neurodegenerative diseases caused by mutations in the BRI ( 2 ) gene. FBD and FDD are characterized by widespread cerebral amyloid angiopathy (CAA), parenchymal amyloid deposition, and neurofibrillary tangles. Transgenic mice expressing wild-type and mutant forms of the BRI(2) protein, Bri ( 2 ) knock-in mutant mice, and Bri ( 2 ) gene knock-out mice have been developed. Transgenic mice expressing a human FDD-mutated form of the BRI ( 2 ) gene have partially reproduced the neuropathological lesions observed in FDD. These mice develop extensive CAA, parenchymal amyloid deposition, and neuroinflammation in the central nervous system. These animal models allow the study of the molecular mechanism(s) underlying the neuronal dysfunction in these diseases and allow the development of potential therapeutic approaches for these and related neurodegenerative conditions. In this review, a comprehensive account of the advances in the development of animal models for FBD and FDD and of their relevance to the study of Alzheimer disease is presented.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Animals
  • Brain / metabolism
  • Brain / pathology*
  • Brain / physiopathology
  • Dementia / genetics*
  • Dementia / pathology*
  • Dementia / physiopathology
  • Disease Models, Animal
  • Gene Knock-In Techniques
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic / genetics*
  • Plaque, Amyloid / genetics
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Itm2b protein, mouse
  • Membrane Proteins