The Impact of Gamma Stimulation on Neurological Phenotypes of Alzheimer's Dementia and Down Syndrome

Abstract

Non-invasive Gamma ENtrainment Using Sensory stimulation (GENUS) at 40Hz reduced Alzheimer’s disease (AD) pathology such as amyloid and tau levels, prevented cerebral atrophy, and improved behavioral testing performance in mouse models of AD. This thesis work focuses on the translation of this intervention into human patients with AD. Initial pilot studies assessed safety, compliance, entrainment and exploratory clinical outcomes in patients with mild AD during acute and chronic exposure to GENUS. Additionally, due to the increase in amyloid burden and other shared biological and cognitive phenotypes present in the setting of trisomy 21 compared to AD, we also present initial investigation into the use of GENUS in adult Ts65Dn mice, a mouse model of Down syndrome (DS). Chronic exposure resulted in significant genetic and immunohistochemical changes related to synapse organization and adult neurogenesis within the hippocampus, as well as an improvement in spatial memory during behavioral testing. Finally, we also share pilot studies in human individuals with DS to show initial safety, compliance, and entrainment data from acute exposure experiments. Overall, GENUS offers a promising, non-invasive method for altering gamma frequency activity in hippocampal and cortical neuronal circuits and improving cognitive performance in the setting of AD and DS.