title: Amyloid and intracellular accumulation of BRI2.
abstract: Familial British dementia (FBD) and familial Danish dementia (FDD) are caused by mutations in the BRI2gene. These diseases are characterized clinically by progressive dementia and ataxia and neuropathologically by amyloid deposits and neurofibrillary tangles. Herein, we investigate BRI2protein accumulation in FBD, FDD, Alzheimer disease and Gerstmann-Sträussler-Scheinker disease. In FBD and FDD, we observed reduced processing of the mutant BRI2pro-protein, which was found accumulating intracellularly in the Golgi of neurons and glial cells. In addition, we observed an accumulation of a mature form of BRI2protein in dystrophic neurites, surrounding amyloid cores. Accumulation of BRI2was also observed in dystrophic neurites of Alzheimer disease and Gerstmann-Sträussler-Scheinker disease cases. Although it remains to be determined whether intracellular accumulation of BRI2may lead to cell damage in these degenerative diseases, our study provides new insights into the role of mutant BRI2in the pathogenesis of FBD and FDD and implicates BRI2as a potential indicator of neuritic damage in diseases characterized by cerebral amyloid deposition.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Holly J
authors.initials: HJ
authors.lastname: Garringer
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Neeraja
authors.initials: N
authors.lastname: Sammeta
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Oblak
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: rvidal@iupui.edu.
authors.forename: Ruben
authors.initials: R
authors.lastname: Vidal
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D028227:Amyloid Neuropathies, Familial; D058227:Amyloidogenic Proteins / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002386:Cataract / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002524:Cerebellar Ataxia / Q000235:genetics* / Q000378:metabolism; D028243:Cerebral Amyloid Angiopathy, Familial / Q000235:genetics* / Q000378:metabolism; D003638:Deafness / Q000235:genetics* / Q000378:metabolism; D003704:Dementia / Q000235:genetics* / Q000378:metabolism; D056726:Genetic Association Studies; D016098:Gerstmann-Straussler-Scheinker Disease / Q000235:genetics / Q000378:metabolism; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics*; D016501:Neurites / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D058227:Amyloidogenic Proteins; C120083:ITM2B protein, human; D008562:Membrane Glycoproteins
keywords: Alzheimer disease; Amyloid; BRI(2); Familial British dementia; Familial Danish dementia; Gerstmann-Sträussler-Scheinker disease