Muscle Cathepsin B Treatment Improves Behavioral and Neurogenic Deficits in a Mouse Model of Alzheimer's Disease.

ABSTRACT: Increasing evidence indicates skeletal muscle function is associated with cognition. Muscle-secreted protease Cathepsin B (Ctsb) is linked to memory in animals and humans, but has an unclear role in neurodegenerative diseases. To address this question, we utilized an AAV-vector-mediated approach to express Ctsb in skeletal muscle of APP/PS1 Alzheimer's disease (AD) model mice. Mice were treated with Ctsb at 4 months of age, followed by behavioral analyses 6 months thereafter. Here we show that muscle-targeted Ctsb treatment results in long-term improvements in motor coordination, memory function, and adult hippocampal neurogenesis, while plaque pathology and neuroinflammation remain unchanged. Additionally, in AD mice, Ctsb treatment normalizes hippocampal, muscle, and plasma proteomic pro

SUBMITTER: Pinto A 

PROVIDER: S-EPMC12610946 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature