Glymphatic system dysfunction and its relationship with neurodegenerative diseases: na integrative literature review

Resumo

This integrative review aimed to synthesize scientific evidence on the relationship between glymphatic system dysfunction and neurodegenerative diseases, contributing theoretical support for advances in prevention, early diagnosis, and clinical management. The study followed Whittemore and Knafl’s methodology and adopted the PICO strategy to guide selection of articles addressing glymphatic alterations and their association with disorders such as Alzheimer’s and Parkinson’s disease. Searches conducted in PubMed, Scopus, Web of Science, SciELO, and LILACS (2015–2025) identified peer-reviewed studies across experimental, clinical, observational, and review designs. The findings consistently demonstrate that impaired glymphatic clearance—driven by AQP4 depolarization, vascular stiffness, sleep disruption, and aging—promotes the accumulation of neurotoxic proteins including β‑amyloid, tau, and α‑synuclein. Evidence also highlights the role of meningeal lymphatic drainage, hydrodynamic forces, and sleep physiology in maintaining clearance efficiency. Emerging imaging biomarkers such as DTI‑ALPS provide promising avenues for early detection of glymphatic impairment, while therapeutic perspectives include improving slow‑wave sleep, optimizing cardiovascular function, and modulating AQP4 organization. Overall, the review indicates that glymphatic dysfunction is a potentially early and modifiable mechanism underlying neurodegeneration, reinforcing its relevance as a target for preventive strategies and disease‑modifying interventions.