Extracellular vesicles contribute to the beneficial effects of exercise training in APP/PS1 mice

Exercise improves cognitive function in Alzheimer’s disease (AD) via mechanism that are not fully clear. Here, we first examined the effect of voluntary exercise training (VET) on energy metabolism and cognitive function in the APP/PS1 transgenic mouse (Tg) model of familial AD. Next, we profiled extracellular vesicles (EVs) and examined whether they may play a role in the protective effects of VET via intranasal administration of EVs, purified from the blood of sedentary (sEV) and/or acutely exercised (eEV) donor wild-type mice into APP/PS1Tg mice. We show that VET reduced resting energy expenditure (REE) and improved cognition in APP/PS1 Tg mice. Administration of eEV, but not sEV, also reduced REE, but had no effect on cognition. Taken together, these data show that exercise is effective intervention to improve symptoms of AD in APP/PS1Tg mice. In addition, eEVs mediate some of these effects, implicating EVs in the treatment of age-related neurodegenerative diseases. [Display omitted] •Exercise restores aberrant resting energy expenditure in APP/PS1 mice•Exercise improves memory and reduces cortical Aβ in APP/PS1 mice•Exercise EVs (eEVs) differ in miRNA and protein cargo, impacting energy metabolism•EVs reduce energy expenditure in APP/PS1 mice but do not improve memory or Aβ Molecular physiology; Neuroscience; Cell biology