tACS for Amyloid-β Reduction in Alzheimer's Disease

Alzheimer's Disease (AD) is characterized by amyloid-β (Aβ) plaque buildup and phosphorylated tau (p-tau) in the brain, as well as widespread neurodegeneration. There is no current treatments that alter disease progression.

Investigators will recruit 20 individuals with AD with evidence of amyloid placques in the brain through Positron Emission Tomography (PET) imaging. Investigators will use a novel approach, transcranial alternating current stimulation (tACS), to target the region of maximum amyloid burden in the brain. All participants will receive tACS. Each individual's participation in the study will consist of approximately 16 visits: 3 days for screening/baseline procedures as described below, 10 tACS study visits, and 3 days for follow-up assessments. Subjects will undergo baseline cognitive assessment, structural and functional MRI characterization, and resting-state EEG measurement. Additionally, patients will undergo a tACS-EEG recording session to assess brain plasticity levels and identify markers of response to stimulation. All subjects will then undergo 10 1-hour sessions of gamma-frequency (40 Hz) tACS, targeted to the region of maximal tracer uptake on the amyloid PET study. Subjects will take a standardized adverse effect questionnaire before and after each session and complete a short cognitive test after each session to demonstrate safety and tolerability. At the end of the 10 sessions, subjects will then repeat the baseline assessments, followed by repeat amyloid PET imaging to assess for changes in amyloid burden.

Investigators anticipate that targeting the region of amyloid burden in the brain with tACS will reduce the amyloid burden as evidence by the follow up PET imaging and show improvement on electrophysiological measures of brain function and on cognitive testing. If our prediction is correct, this will will provide a critical first step in the development of a novel intervention to prevent and treat AD.