Modeling familial British and Danish dementia.
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.
Garringer
Holly J
HJ
Department of Pathology and Laboratory Medicine, Indiana Alzheimer Disease Center, Indiana University School of Medicine, 635 Barnhill Drive MSB A136, Indianapolis, IN, 46202, USA.
Murrell
Jill
J
D'Adamio
Luciano
L
Ghetti
Bernardino
B
Vidal
Ruben
R
D048868:Adaptor Proteins, Signal Transducing; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D003704:Dementia / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D055879:Gene Knock-In Techniques; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic / Q000235:genetics*; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; C492300:Itm2b protein, mouse; D008565:Membrane Proteins