Adolescent Chronic Sleep Deprivation and Alzheimer's Risks: Impacts on Glymphatic Clearance, Synaptic Plasticity, and Neuroinflammation

Adolescence represents a critical neurodevelopmental window characterized by peak metabolic demands and the maturation of key brain regions. While the link between sleep disruption and Alzheimer's disease risk is well-documented in older adults, chronic sleep deprivation during the high plasticity period may destabilize the mechanistic foundations of long-term brain health. This review identifies two pathological trajectories: firstly, a functional collapse of the glymphatic system and astrocytic AQP4 polarization leading to proteostatic failure; and second, disruption in synaptic plasticity and the lowering of the brain's inflammatory threshold. Notably, subjective neurobehavioral restoration marks persistent metabolic and vascular deficits that fail to return to baseline even after recovery sleep. Therefore, prioritizing sleep consistency in adolescents is a potent non-invasive strategy for preserving cognitive reserve and reducing Alzheimer’s disease risk.