Preventing Alzheimer's May Start at Night: Study Links Sleep to Overnight Clearing of Alzheimer's-Linked Proteins

A landmark randomized crossover study in humans by researchers at Applied Cognition links sleep-related glymphatic activity to blood biomarker shifts for amyloid beta and tau. The researchers say the pattern is consistent with overnight movement of these proteins out of the brain and into the bloodstream, supporting the rationale for a new therapeutic approach to Alzheimer's disease.

Key findings:

• The researchers found that sleep (vs. sleep deprivation) was associated with higher morning blood levels of amyloid beta and tau, two proteins linked to Alzheimer's disease, suggesting that during normal sleep these proteins were cleared from brain tissue overnight into the bloodstream.
• Using overnight monitoring of brain activity, blood-flow signals and interstitial fluid shifts, the researchers found that the sleep vs. sleep-deprivation differences in morning amyloid beta and tau levels are consistent with increased glymphatic clearance, the brain's fluid-based "clean-up" system.
• The findings highlight glymphatic function as a potentially therapeutic target for Alzheimer's disease.

SAN FRANCISCO, Jan. 27, 2026 /PRNewswire/ -- What if sleep could help prevent Alzheimer's disease? A new landmark study by researchers at Applied Cognition, a clinical-stage therapeutic company, points to the brain's glymphatic system, its fluid-based "clean-up" pathway, as a key driver of overnight clearance of Alzheimer's-linked proteins. The researchers found that during normal sleep, levels of amyloid beta and tau, two proteins linked to Alzheimer's disease, were higher in next-morning blood samples, a pattern they interpret as consistent with movement out of brain tissue and into the bloodstream.

The study, published today in Nature Communications, provides the strongest evidence to date that sleep-driven physiological processes play a key role in removing toxic proteins long linked to neurodegeneration.

In a randomized crossover trial of 39 participants, researchers showed that normal sleep significantly increased morning plasma levels of amyloid beta and tau compared to sleep deprivation. The researchers found that these elevations indicate enhanced overnight clearance from brain tissue, a long-hypothesized mechanism now directly demonstrated in humans.

"This study confirms something profoundly important, that the human brain has an active, sleep-driven clearance system, and when sleep neurophysiology is disrupted, that system fails," said Dr. Paul Dagum, CEO and co-founder of Applied Cognition. "These findings directly validate Applied Cognition's therapeutic strategy to enhance glymphatic clearance as a disease-modifying approach for early Alzheimer's disease."

The study paired advanced plasma biomarker analysis with continuous overnight monitoring of brain electrical activity (EEG), cerebrovascular dynamics, and neurophysiological measures of fluid transport captured using the company's novel device, recently validated in a study published in Nature Biomedical Engineering. According to the researchers, the combined measurements pointed to a distinct sleep-related glymphatic signature, including deep-sleep EEG patterns, increased cerebrovascular pulsatility, and decreased resistance to fluid flow within the brain.

"Our findings provide the first causal human evidence that sleep-active glymphatic transport clears amyloid beta and tau," said Dr. Jeffrey Iliff, Professor of Psychiatry at the University of Washington School of Medicine, who along with Dr. Maiken Nedergaard first characterized the glymphatic system in animal models. "This work brings together over a decade of research in rodents supporting a role for glymphatic transport in the clearance of amyloid beta and tau from the brain and shows that these same processes are indeed operating in the human brain."

The results position glymphatic function as a powerful, modifiable therapeutic target reinforcing Applied Cognition's strategy of developing interventions that enhance the brain's intrinsic clearance pathways. By linking sleep physiology, biomarker dynamics, and glymphatic transport in humans, the study marks a pivotal advance in Alzheimer's disease prevention, early detection, and treatment.

The paper's authors include Paul Dagum, Donald Elbert, Laurent Giovangrandi, Tarandeep Singh, Venky Venkatesh, Alejandro Corbellini, Robert Kaplan, Swati Rane Levendovszky, Elizabeth Ludington, Kevin Yarasheski, Jeffrey Lowenkron, Carla VandeWeerd, Miranda Lim and Jeffrey Iliff.

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About Applied Cognition
Applied Cognition is clinical-stage platform therapeutics company advancing the brain's glymphatic system to drug development. Enhancing glymphatic function is a promising new therapeutic strategy for treating neurodegenerative diseases. Using its first-in-class platform with continuous monitoring of glymphatic activity in humans, the company has successfully identified the first therapeutic target and its lead drug candidate to enhance glymphatic clearance of amyloid and tau. Applied Cognition is currently advancing its program for early-stage Alzheimer's and expanding its pipeline to explore treatments for other conditions.

SOURCE Applied Cognition