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Osteoblastic Swedish mutant APP expedites brain deficits by inducing endoplasmic reticulum stress-driven senescence.
Pan, Jin-Xiu; Sun, Dong; Lee, Daehoon; Xiong, Lei; Ren, Xiao; Guo, Hao-Han; Yao, Ling-Ling; Lu, Yuyi; Jung, Caroline; Xiong, Wen-Cheng.
Affiliation
  • Pan JX; Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
  • Sun D; Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA.
  • Lee D; Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
  • Xiong L; Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
  • Ren X; Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA.
  • Guo HH; Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
  • Yao LL; Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA.
  • Lu Y; Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
  • Jung C; Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
  • Xiong WC; Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Commun Biol ; 4(1): 1326, 2021 11 25.
Article in En | MEDLINE | ID: mdl-34824365
Patients with Alzheimer's disease (AD) often have osteoporosis or osteopenia. However, their direct link and relationship remain largely unclear. Previous studies have detected osteoporotic deficits in young adult Tg2576 and TgAPPsweOCN mice, which express APPswe (Swedish mutant) ubiquitously and selectively in osteoblast (OB)-lineage cells. This raises the question, whether osteoblastic APPswe contributes to AD development. Here, we provide evidence that TgAPPsweOCN mice also exhibit AD-relevant brain pathologies and behavior phenotypes. Some brain pathologies include age-dependent and regional-selective increases in glial activation and pro-inflammatory cytokines, which are accompanied by behavioral phenotypes such as anxiety, depression, and altered learning and memory. Further cellular studies suggest that APPswe, but not APPwt or APPlon (London mutant), in OB-lineage cells induces endoplasmic reticulum-stress driven senescence, driving systemic and cortex inflammation as well as behavioral changes in 6-month-old TgAPPsweOCN mice. These results therefore reveal an unrecognized function of osteoblastic APPswe to brain axis in AD development.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Phenotype / Brain / Cellular Senescence / Amyloid beta-Protein Precursor / Alzheimer Disease Limits: Animals / Humans / Male Language: En Journal: Commun Biol Year: 2021 Document type: Article Affiliation country: Estados Unidos Country of publication: Reino Unido

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Phenotype / Brain / Cellular Senescence / Amyloid beta-Protein Precursor / Alzheimer Disease Limits: Animals / Humans / Male Language: En Journal: Commun Biol Year: 2021 Document type: Article Affiliation country: Estados Unidos Country of publication: Reino Unido