Document Detail

APPswe/Aβ regulation of osteoclast activation and RAGE expression in an age dependent manner.
MedLine Citation:
PMID:  21105076     Owner:  NLM     Status:  Publisher    
Alzheimer's disease (AD), one of the most dreaded neurodegenerative disorders, is characterized by cortical and cerebrovascular Aβ (amyloid β peptide) deposits, neurofibrillary tangles, chronic inflammation, and neuronal loss. Increased bone fracture rates and reduced bone density are commonly observed in patients with AD, suggesting a common denominator(s) between both disorders. However, very few studies are available that have addressed this issue. Here, we present evidence for a function of amyloid precursor protein (APP) and Aβ in regulating osteoclast (OC) differentiation in vitro and in vivo. Tg2576 mice, which expresses Swedish mutation of APP (APPswe) under the control of prion promoter (1,2), exhibit biphasic effects on OC activation, with an increase of OC in younger mice (< 4 month old), but a decrease in older Tg2576 mice (> 4 month old). The increase of OC in young Tg2576 mice appears to be mediated by Aβ oligomers and RAGE (receptor for advanced glycation end products) expression in BMMs. However, the decrease of OC formation and activity in older Tg2576 mice may be due to the increase of sRAGE in aged Tg2576 mice, an inhibitor of RANKL induced osteoclastogenesis. These results suggest an unexpected function of APPswe / Aβ, reveal a mechanism underlying altered bone remodeling in AD patients, and implicate APP/Aβ and RAGE as common denominators for both AD and osteoporosis. © 2010 American Society for Bone and Mineral Research.
Shun Cui; Fei Xiong; Yan Hong; Ji-Ung Jung; Xing-Sheng Li; Jian-Zhong Liu; Riqiang Yan; Lin Mei; Xu Feng; Wen-Cheng Xiong
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-11-23
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  -     ISSN:  1523-4681     ISO Abbreviation:  -     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Institute of Molecular Medicine & Genomics and Department of Neurology Medical College of Georgia, Augusta, GA 30912.
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