Narrative review reveals therapeutic targets within brain lymphatic clearance pathways in Alzheimer's disease, highlighting novel strategies to enhance metabolic waste removal.
With the acceleration of global aging, the relationship between Alzheimer's disease (AD) and the glymphatic system (GS) has become a research hotspot in the field of neuroscience in recent years. Traditionally, the central nervous system was thought to lack a lymphatic system; however, research over the past decade has overturned this view. Studies have revealed the existence of GS and meningeal lymphatic vessels (mLVs) in the brain, which clear metabolic waste (such as amyloid-β and tau proteins) through the exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF). Dysfunction of the GS can lead to abnormal deposition of pathological proteins, which may trigger or exacerbate AD. Currently, the association between the GS and AD treatment mainly focuses on drug development (such as small molecules that promote glymphatic circulation), physical therapies (such as 40 Hz photoacoustic therapy), and surgical interventions (primarily deep cervical lymphatic-vein anastomosis and cranial bone maneuver), all of which are under exploration. With the precision of diagnostic technologies and the targeting of therapeutic methods, future intervention strategies surrounding GS may become a significant breakthrough in overcoming the treatment impasse of AD, bringing new hope to tens of millions of AD patients worldwide.
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Song et al. (2026) studied this question.
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