Alzheimer’s disease (AD) begins developing decades before noticeable clinical symptoms appear. Understanding what happens during this preclinical phase is an ongoing research priority, because if scientists can identify brain changes that occur before symptoms appear, it could enable earlier detection and intervention.
Sleep provides a unique window into the silent, preclinical stage, as the brain’s electrical activity during sleep can reveal early signs of “stress” that appear as brief surges of abnormal electrical activity known as hyperexcitability. Drs. Osorio and Lisgaras believe that monitoring brain activity during sleep could uncover patterns associated with the early development of AD.
An electroencephalogram (EEG) is a non-invasive way to measure the brain’s activity. It uses a cap fitted with special electrodes that detect and record the brain’s electrical signals. The Osorio and Lisgaras labs plan to use sleep EEG data to explore whether changes in brain activity can be tied to early changes in AD. The labs also have access to a specialized sleep EEG that can detect activity outside the range of a typical EEG. They are interested in identifying ultra-fast brain waves, called high-frequency oscillations (HFOs), and examining how they relate to AD biomarkers and epileptiform activity. They hypothesize that identifying brain activity signatures associated with AD progression will enable targeted interventions with FDA-approved drugs capable of normalizing brain activity.
This project breaks down into three aims. In the first aim, the teams will use sleep EEG data from several existing cohorts of cognitively normal older adults to examine whether conventional epileptiform signals (hyperexcitability) are associated with Alzheimer’s biomarkers in the blood. While these individuals may not yet show symptoms of AD, blood biomarkers change well before cognitive symptoms arise. This will allow the labs to link any abnormal brain activity they observe with these early AD biomarker changes. For the second aim, a subset of patients with the highest risk of developing AD and a group of age-matched controls will be asked to participate in a detailed study using the specialized sleep EEG to measure HFOs. In the final aim, they will determine how these different electrical signatures relate to one another and whether they reflect the same underlying AD brain changes or represent distinct pathways to disease.
The goal of this work is to identify individuals with hyperexcitability-driven pathology as early as possible as they could benefit from targeted interventions. Because FDA-approved medications that normalize brain excitability are safe and available, the findings could rapidly enable personalized prevention strategies—matching the right treatment to the right person based on their brain’s electrical signature during sleep, several years before symptoms appear.
