Amyloid and intracellular accumulation of BRI2

NEUROBIOLOGY OF AGING

卷:52

Article

Garringer, Holly J.^1,2  Sammeta, Neeraja¹  Oblak, Adrian^1,2  Ghetti, Bernardino^1,2  Vidal, Ruben^1,2 

[1] Indiana Univ Sch Med, Dept Pathol & Lab Med, 635 Barnhill Dr MSB A136, Indianapolis, IN 46202 USA

[2] Indiana Univ Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA

关键词: BRI2;    Amyloid;    Familial British dementia;    Familial Danish dementia;    Alzheimer disease;    Gerstmann-Straussler-Scheinker disease;   

DOI  :  10.1016/j.neurobiolaging.2016.12.018

来源: Elsevier

【 摘 要 】

Familial British dementia (FBD) and familial Danish dementia (FDD) are caused by mutations in the BRI2 gene. These diseases are characterized clinically by progressive dementia and ataxia and neuro-pathologically by amyloid deposits and neurofibrillary tangles. Herein, we investigate BRI2 protein accumulation in FBD, FDD, Alzheimer disease and Gerstmann-Straussler-Scheinker disease. In FBD and FDD, we observed reduced processing of the mutant BRI2 pro-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 BRI2 protein in dystrophic neurites, surrounding amyloid cores. Accumulation of BRI2 was also observed in dystrophic neurites of Alzheimer disease and Gerstmann-Straussler-Scheinker disease cases. Although it remains to be determined whether intracellular accumulation of BRI2 may lead to cell damage in these degenerative diseases, our study provides new insights into the role of mutant BRI2 in the pathogenesis of FBD and FDD and implicates BRI2 as a potential indicator of neuritic damage in diseases characterized by cerebral amyloid deposition. (C) 2016 Elsevier Inc. All rights reserved.

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