Muscular Swedish mutant APP-to-Brain axis in the development of Alzheimer's disease.
Cell Death Dis
; 13(11): 952, 2022 11 10.
Article
in En
| MEDLINE
| ID: mdl-36357367
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, TgAPPsweHSA, by crossing LSL (LoxP-STOP-LoxP)-APPswe with HSA-Cre mice, which express APPswe (Swedish mutant APP) selectively in skeletal muscles. Examining phenotypes in TgAPPsweHSA 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 APPswe 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 APPswe to brain in AD development.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sarcopenia
/
Alzheimer Disease
Type of study:
Prognostic_studies
Limits:
Animals
Country/Region as subject:
Europa
Language:
En
Journal:
Cell Death Dis
Year:
2022
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Reino Unido