Oligodendrocyte precursors (OPCs) possess numerous processes and neurons are abundantly distributed in the brain. We wondered whether OPCs form other types of contact with neurons, apart from synapses. Immunohistochemical analysis exhibited that OPC processes contact somata of inhibitory and excitatory neurons equally well, with preference for active neurons. In addition, more contacts were observed when neurons were chemogenetically stimulated. Utilizing stimulated emission depletion (STED) microscopy, lysosomes were identified in the neuronal compartment at the contact site, particularly the smaller lysosomes located closer to the point of contact. Therefore, we hypothesized that OPCs might selectively promote neuronal lysosome release. Indeed, tracking lysosomes in neuron-OPC co-cultures confirmed their attraction to and release at the contact site. Selective expression of mScarlet-I in neuronal lysosomes revealed their appearance in OPC processes, suggesting not only a selective OPC process-evoked release of lysosomes from neurons, but also their uptake by OPC, indicative of a neuron-OPC signal exchange. To investigate the biological significance of OPC-mediated lysosome release, we utilized NG2-CreERT2xCav1.2/Cav1.3flox mice that display a reduced branching of OPC processes. Indeed, mutant mice exhibited fewer neuron-OPC contacts, larger lysosome accumulation in neuronal somata, altered neuronal activity and increased numbers of senescent neurons in aging. A similar reduction in OPC branching and lysosome accumulation were observed in an early-stage Alzheimer's disease mouse model, linking OPC-neuron contact to neurodegeneration. In summary, OPC processes modulate neuronal activity by facilitating lysosome release through direct interaction at the lysosome releasing sites on neuronal somata, presenting a prospective therapeutic avenue for addressing Alzheimer's disease.