Cover
Volume 6, Issue 3 (2026) – 6 articles
Cover Picture: The glymphatic system is a brain-wide waste clearance network responsible for eliminating metabolic byproducts, including amyloid-beta (Aβ) and tau, two major pathological hallmarks of Alzheimer’s disease (AD). This review synthesizes current evidence indicating that glymphatic dysfunction, driven by structural and molecular impairments in meningeal lymphatic vessels, perivascular spaces, and aquaporin-4 (AQP4) channels, plays a critical role in the pathogenesis and progression of AD. Multiple contributing factors, including aging, sleep disturbances, and genetic susceptibility such as apolipoprotein E4 (APOE4), further aggravate glymphatic impairment, thereby promoting Aβ accumulation, neuroinflammation, and cognitive decline. Emerging therapeutic strategies aimed at restoring glymphatic function include pharmacological interventions, such as melatonin, cilostazol, and vascular endothelial growth factor C (VEGF-C), as well as traditional Chinese medicine approaches, including Borneol and Yuanzhi Powder, and neuromodulation-based therapies such as focused ultrasound and electroacupuncture. In addition, lifestyle interventions, particularly physical exercise and sleep optimization, may enhance cerebrospinal fluid (CSF) dynamics and preserve AQP4 polarization, thereby facilitating metabolic clearance. Preclinical studies have demonstrated that these interventions can reduce Aβ and tau deposition, suppress neuroinflammation, and improve cognition. However, substantial clinical validation remains necessary before these findings can be translated into effective therapeutic applications. Collectively, this review highlights the glymphatic system as a promising therapeutic target for AD and provides an integrated perspective linking mechanistic insights with emerging therapeutic strategies.
