Applied Cognition, a clinical-stage platform therapeutic company, and academic partners have published the first continuous, non-invasive measurements of the human glymphatic system in Nature Biomedical Engineering. The glymphatic system is a brain-wide waste-clearance network that removes toxic proteins including amyloid-β and tau during sleep. Dysfunction of the system is implicated in Alzheimer’s disease and other neurodegenerative conditions.
The research, conducted in partnership with researchers at the University of Florida and the University of Washington, studied 44 healthy older adults (ages 49-66) across nights of normal sleep and sleep deprivation. Applied Cognition’s novel multimodal electrical impedance spectroscopy device was validated against contrast-enhanced MRI, the current gold standard. The wearable device measures brain parenchymal resistance, a marker of glymphatic function, every two minutes, compared to hours required for MRI scans. The study found that parenchymal resistance decreased by approximately 20% during sleep, correlating with enhanced waste clearance.
This technology has already helped identify a promising drug candidate that improves glymphatic clearance and is now in early clinical trials for Alzheimer’s disease.
“This work is pivotal in defining the role glymphatic dysfunction plays in Alzheimer’s and discovering therapies to rescue it,” said Dr. Paul Dagum, CEO and co-founder of Applied Cognition, in a release.
Previously, studying the glymphatic system’s function in humans required invasive procedures or was limited to infrequent, expensive MRI scans performed in specialized facilities. Applied Cognition’s ear-mounted device offers a scalable option for continuous, real-time monitoring in natural sleep environments. The technology captures the dynamic relationship between sleep stages, brain rhythms, heart rate, and glymphatic function with unprecedented temporal resolution.
“This unlocks our ability to study glymphatic function in the real world and with high-temporal resolution, not just the MRI suite, giving us new mechanistic insights of its role in neurological and psychiatric conditions,” said Dr. Jeffrey J. Iliff, in a press release.
Applied Cognition is advancing its lead drug program for early-stage Alzheimer’s and expanding its pipeline across neurodegenerative and psychiatric disorders.
The study’s findings align with preclinical research showing that glymphatic function is enhanced by increased EEG delta power and reduced beta power during sleep, as well as lower heart rates.
The paper’s authors include Paul Dagum, Laurent Giovangrandi, Swati Rane Levendovszky, Jake J. Winebaum, Tarandeep Singh, Yeilim Cho, Robert M. Kaplan, Michael S. Jaffee, Miranda M. Lim, Carla Vandeweerd, and Jeffrey J. Iliff.
Filed Under: Neurological Disease
