Boosting slow-wave activity (SWA) by modulating slow waves through closed-loop auditory stimulation (CLAS) might provide a powerful non-pharmacological tool to investigate the link between sleep and neurodegeneration. Here, we established mouse CLAS (mCLAS)-mediated SWA enhancement and explored its effects on sleep deficits in neurodegeneration, by targeting the up-phase of slow waves in mouse models of Alzheimer's disease (AD, Tg2576) and Parkinson's disease (PD, M83). We found that tracking a 2 Hz component of slow waves leads to highest precision of non-rapid eye movement (NREM) sleep detection in mice, and that its combination with a 30° up-phase target produces a significant 15-30% SWA increase from baseline in wild-type (WT