期刊
NEUROBIOLOGY OF AGING
卷 67, 期 -, 页码 148-158出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2018.03.021
关键词
Tauopathy; Alzheimer's disease; Wnt proteins; Bone mineral density; Beta catenin; Neurodegeneration
资金
- National Science Foundation [NSF-CMMI1537745]
- Northeast Ohio Medical University
Low bone mineral density (BMD) is a significant comorbidity in Alzheimer's disease (AD) and may reflect systemic regulatory pathway dysfunction. Low BMD has been identified in several AD mouse models selective for amyloid-beta or tau pathology, but these deficits were attributed to diverse mechanisms. In this study, we identified common pathophysiological mechanisms accounting for bone loss and neurodegeneration in the htau mouse, a tauopathy model with an early low BMD phenotype. We investigated the Wnt/beta-catenin pathwayda cellular signaling cascade linked to both bone loss and neuropathology. We showed that low BMD persisted in male htau mice aged from 6 to 14 months, remaining significantly lower than tau-null and C57BL/6J controls. Osteogenic gene expression in female and male htau mice was markedly reduced from controls, indicating impaired bone remodeling. In both the bone and brain, htau mice showed alterations in Wnt/b-catenin signaling genes suggestive of increased inhibition of this pathway. These findings implicate dysfunctional Wnt signaling as a potential target for addressing bone loss in AD. (C) 2018 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据