| First Author | Pan JX | Year | 2022 |
| Journal | Cell Death Dis | Volume | 13 |
| Issue | 11 | Pages | 952 |
| PubMed ID | 36357367 | Mgi Jnum | J:341736 |
| Mgi Id | MGI:7385256 | Doi | 10.1038/s41419-022-05378-4 |
| Citation | Pan JX, et al. (2022) Muscular Swedish mutant APP-to-Brain axis in the development of Alzheimer's disease. Cell Death Dis 13(11):952 |
| abstractText | Alzheimer's disease (AD) is the most common form of dementia. Notably, patients with AD often suffer from severe sarcopenia. However, their direct link and relationship remain poorly understood. Here, we generated a mouse line, TgAPP(swe)(HSA), by crossing LSL (LoxP-STOP-LoxP)-APP(swe) with HSA-Cre mice, which express APP(swe) (Swedish mutant APP) selectively in skeletal muscles. Examining phenotypes in TgAPP(swe)(HSA) mice showed not only sarcopenia-like deficit, but also AD-relevant hippocampal inflammation, impairments in adult hippocampal neurogenesis and blood brain barrier (BBB), and depression-like behaviors. Further studies suggest that APP(swe) expression in skeletal muscles induces senescence and expressions of senescence-associated secretory phenotypes (SASPs), which include inflammatory cytokines and chemokines; but decreases growth factors, such as PDGF-BB and BDNF. These changes likely contribute to the systemic and hippocampal inflammation, deficits in neurogenesis and BBB, and depression-like behaviors, revealing a link of sarcopenia with AD, and uncovering an axis of muscular APP(swe) to brain in AD development. |
