Sleep as Medicine: How Deep Rest Defends Against Alzheimer’s
Sleep is a form of nightly neuroprotection.
👋 Welcome to this edition of Sleepletter™ where we offer you easy-to-read insights from the latest research papers from the field of sleep neurobiology and clinical sleep medicine. Sign up to also receive Sleepletter by email.
🏆 Want to optimize your sleep or attend my "Ask Me Anything" session? Join us for exclusive seminars and events that unveil the science of sleep and receive personalized, actionable and science-backed recommendations how to improve sleep. Subscribe here!
We often think of sleep as a passive state—something we do when the brain shuts down for the night. But modern neuroscience is painting a radically different picture: during sleep, especially deep non-REM (e.g. slow-wave) sleep, the brain engages in an set of restorative processes that may actively defend against diseases like Alzheimer’s.
Let’s start with what we know about Alzheimer’s disease (AD). One of its earliest hallmarks is the accumulation of abnormal proteins in the brain—namely beta-amyloid (Aβ) and tau. These sticky proteins clump together and interfere with brain function, particularly in areas of the brain responsible for memory and cognition. What’s striking is that these proteins begin accumulating years—even decades—before symptoms appear.
So where does sleep come in? Disrupted sleep may not just be a symptom of Alzheimer’s—it might help drive it. Poor sleep—especially reduced deep (slow-wave) sleep—has been linked to increased levels of Aβ and tau in the brain. Deep sleep acts like a nightly rinse cycle, clearing out toxic proteins via the so called brain’s glymphatic system. This system is a recently discovered waste clearance network that becomes especially active during deep sleep. It works by circulating cerebrospinal fluid through brain tissue, flushing out metabolic waste—including amyloid-β and tau proteins, which are key culprits in Alzheimer’s disease. When we don't get enough restorative sleep, that cleaning process stalls—and the waste begins to pile up.
And it doesn’t take much. Just a single night of sleep deprivation in healthy middle-aged adults can raise levels of Aβ42, tau, and even α-synuclein—three key proteins associated with neurodegenerative diseases. In animal studies, chronic sleep loss accelerates the buildup of these proteins, especially in genetically vulnerable brains.
Worse still, as these proteins accumulate, they begin targeting brain regions that regulate sleep itself, setting off a vicious cycle: poor sleep leads to more pathology, which damages sleep centers, which then further disrupts sleep. It’s a biological feedback loop that researchers now believe may begin years before memory loss is evident.
The data gets more sobering. In one large study, older adults who slept just two hours less per night had a significantly increased risk of developing dementia, especially Alzheimer’s. Another study found that those with high sleep fragmentation had a 1.5-times greater risk of developing cognitive symptoms due to Alzheimer’s over the next three years—even if they appeared healthy at baseline.
What’s even more fascinating is that sleep may help offset the genetic risk of Alzheimer’s. People with the APOE4 gene—a major genetic risk factor for Alzheimer’s—are more likely to show early signs of the disease if they also have poor sleep. But in APOE4 carriers who slept well, that risk was notably reduced. And in rare cases, people with certain “natural short sleeper” genes sleep fewer than 6.5 hours per night yet show no increased risk of Alzheimer’s. In mice, those same genes actually reduced tau and amyloid plaque buildup, hinting that sleep quality and efficiency may matter just as much—if not more—than total sleep duration.
The encouraging news is that sleep doesn’t just reveal risk—it might also offer protection. Boosting deep sleep in mouse models reduces toxic protein accumulation. In people, better sleep quality has been linked to sharper memory, better executive function, and even delayed onset of dementia.
The bottom line: sleep isn’t a luxury, it’s a key pillar of mental and physical health and in this article we’ve covered only a tiny (but crucial) piece of it’s importance. Sleep is a form of nightly neuroprotection—one that might just be our best natural defense against Alzheimer’s and other neurodegenerative diseases.
***
About the author
Alen Juginović is a medical doctor and postdoctoral researcher in the Department of Neurobiology at Harvard Medical School studying the effect of poor sleep quality on health. He is a member of the Editorial Board of the Journal of Clinical Sleep Medicine, the official journal of the American Academy of Sleep Medicine. As a keynote speaker at conferences and teacher at Harvard College, he often discusses sleep's importance during the educational process and in media appearances. Alen is also focused on personalized sleep optimization for individuals and athletes (e.g. jet lag management), as well as being an advisor/investor/consultant for companies and individuals in the sleep field. He leads a team at Med&X Association organizing international award-winning conferences, including the Plexus Conference, which drew over 2,400 participants from 30+ countries, featuring 10 Nobel laureates and medical leaders. Med&X also collaborates with research labs and clinics from leading universities and hospitals around the world offering invaluable internships to help accelerate the development of top medical students, physicians and scientists. Feel free to contact Alen via LinkedIn for any inquiries.
Disclaimer: The content provided in this newsletter is for informational and educational purposes only. It is not intended as medical or professional advice. The reader should consult with a medical professional for medical conditions or concerns, and with a financial or legal professional regarding any other specific needs or inquiries they may have related to the material discussed.
The writer expressly disclaims responsibility, obligation, or liability for actions taken by the reader in their unique circumstances based on any guidance, suggestions or recommendations made in this newsletter related to sleep health, optimization or hygiene. This content is not a substitute for personalized medical diagnosis, treatment or care from a trained physician.
The writer has made good faith efforts to confirm that all sleep science, research or health statistics referenced from third party sources are accurately represented. However, no warranty is made as to completeness or ongoing accuracy. Readers agree any reliance on newsletter content for decision making is at their sole discretion and risk. The writer is released of liability or claims related to applied use of this general educational content on sleep physiology or best practices.
Cartoon images generated with Adobe Firefly.