A recent debate at the 2025 SLEEP Annual Meeting challenged longstanding assumptions about the role of sleep-dependent brain clearance in Alzheimer disease (AD). Dr. Andrew Varga, a neuroscientist and physician at Mount Sinai, participated in the discussion to provide insights on the topic.
The glymphatic system, which relies on cerebrospinal fluid flowing through interstitial spaces during slow-wave sleep, is responsible for clearing metabolic waste and neurotoxic proteins from the brain. However, research suggests that wakefulness may play a greater role in this clearance process than previously thought.
Historical evidence supports the idea that sleep promotes waste clearance in the brain, but newer studies propose alternative theories. Dr. Varga explained that while the glymphatic system is crucial for clearing beta-amyloid and tau proteins associated with neurodegenerative diseases like AD, wakefulness may also contribute to clearance.
The debate highlights the need for more research on measuring brain clearance in humans and exploring complementary mechanisms that may contribute to AD risk. Emerging therapeutic strategies aim to enhance glymphatic function, including pharmacological interventions such as dual orexin receptor antagonists and technological interventions like transcranial magnetic or electrical stimulation.
To prevent Alzheimer’s progression, it is essential to focus on good sleep hygiene, including identifying and treating sleep disorders like apnea or insomnia. Interventions can be categorized into pharmacology, technology, and environmental modifications. While the exact mechanisms remain speculative, research suggests a link between sleep disruption and AD, with potential contributions from the glymphatic system, neural activity, and immune system.
Further investigation is necessary to understand how much each mechanism contributes and where intervention might be most effective.
Source: https://www.neurologylive.com/view/neurovoices-andrew-varga-debating-whether-brain-cleansing-prevents-alzheimer-disease