Young Blood Rescues the Cognition of Alzheimer's Model Mice by Restoring the Hippocampal Cholinergic Circuit.

An increasing number of studies have demonstrated the benefits of young individual-derived blood for aging-related diseases. However, the effects of young blood on the cognitive and cholinergic transmission defects in aging-associated Alzheimer's disease (AD) remain elusive. In the current study, we showed that young blood serum delivered intravenously attenuated deficits in hippocampal-dependent learning and memory, alleviated hippocampal Aβ plaque pathology, restored synapse formation and synaptic plasticity, repaired the hippocampal cholinergic circuit, and triggered several canonical neuroprotective mechanisms [including repressor element 1-silencing transcription factor (REST)/Forkhead box protein O1 (FOXO1) signaling] in aged AD model mice. However, pharmacological blockage of hippocampal cholinergic activity nearly abrogated the neuroprotective actions of young blood serum in AD mice. Thus, our findings suggest that exogenous young blood serum exerts therapeutic effects on AD-associated cognitive disorders and pathology by promoting hippocampal cholinergic input and simultaneously activating other neuroprotective mechanisms.