Sleep-neuroinflammation interactions in Alzheimer's disease: a systematic review of biomarker pathways

Although sleep disturbances are increasingly associated with Alzheimer's disease (AD), the mechanistic interplay between sleep physiology, neuroinflammation and AD-related pathology is not fully understood. The question of whether disrupted sleep contributes to neurodegeneration or merely reflects early pathological processes is still being debated. In accordance with PRISMA-2020 guidelines, we conducted a systematic review to synthesize the current evidence linking objectively measured sleep alterations, glial activation and AD-related outcomes. A comprehensive search of PubMed, Scopus, EMBASE and Web of Science (January 2000 - June 2026) identified 40 original studies that met the predefined inclusion criteria. These studies included objective sleep assessments (polysomnography, electroencephalography, actigraphy, or experimental sleep manipulation), direct evaluations of neuroinflammatory or glial markers, and assessments of amyloid-β (Aβ), tau pathology, neurodegeneration and cognition. Human studies indicate that slow-wave sleep impairment, sleep fragmentation, and REM sleep dysregulation are linked to neuroinflammation and AD-related pathology. Further mechanistic insights come from experimental animal and translational studies, which show that sleep deprivation or disruption may enhance microglial activation, astrocytic reactivity, and the accumulation of AD-related proteins. However, limited prior work has integrated evidence from sleep physiology, central neuroinflammatory measures, and multimodal AD biomarkers in humans. The available evidence supports a biologically plausible, potentially bidirectional relationship between sleep disruption and AD pathology, while highlighting important gaps in translation. Further longitudinal and interventional investigations are required to clarify causality and determine whether targeting sleep physiology could meaningfully influence disease trajectories.