期刊
NEUROBIOLOGY OF AGING
卷 35, 期 7, 页码 1596-1604出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2014.01.007
关键词
Alzheimer's disease; BRI2; Amyloid plaques; Human hippocampus; Pathogenesis
资金
- Erasmus Mundus Joint Doctorate Program (EMJD 2009-2013, Action 1B) [159302-1-2009- 1-NL-ERA]
- German scientific network for dementia research [BMBF 01GI1010C]
BRI2 protein binds amyloid precursor protein to halt amyloid-beta production and inhibits amyloid-b aggregation via its BRICHOS-domain suggesting a link between BRI2 and Alzheimer's disease (AD). Here, we investigate the possible involvement of BRI2 in human AD pathogenesis. BRI2 containing BRICHOS-domain was increased up to 3-fold in AD hippocampus (p = 0.003, n = 14/group). Immunohistochemistry showed BRI2 deposits associated with amyloid-b plaques in early pathologic stages (Braak-III; Thal-2/3). We observed a decrease in the protein levels of ADAM10 (p = 0.02) and furin (p = 0.066), as well as an increase in SPPL2b (p < 0.0001) in AD hippocampus. Because these enzymes are involved in BRI2 processing, their changes may lead to aberrant processing of BRI2 promoting its deposition and likely affecting BRI2 function. Loss of BRI2 function in AD was supported by the decreased presence of BRI2-amyloid precursor protein complexes in the hippocampus of AD patients compared with control subjects. In conclusion, our data obtained from human samples indicate that in early stages of AD there is an increased deposition of BRI2, which likely leads to impaired BRI2 function thereby influencing AD pathophysiology. (C) 2014 Elsevier Inc. All rights reserved.
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