The combination of anti-amyloid therapy and rTMS for AD - PROJECT SUMMARY / ABSTRACT Many individuals suffer from dementia-related cognitive impairment due to Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD). This number is expected to grow as the population ages and lifespan increases. Developing effective treatment strategies is of the upmost importance, as this impairment places a huge burden on the patients themselves, their caregivers, and healthcare resources. The newest monoclonal antibody treatments can reduce amyloid accumulation but with only a modest impact on cognitive decline. However, repetitive transcranial magnetic stimulation (rTMS) is a promising treatment strategy that utilizes electromagnetics to noninvasively activate cortical cells and restore cognitive function. We believe that amyloid must be reduced in order to maximize the memory-boosting effect of rTMS. Therefore, combining a pharmacological intervention to reduce plaque accumulation with brain stimulation to restore cognition could prove to be an effective treatment strategy for the multi-dimensional components to MCI and AD. This proposal aims to systematically test the combined effects of anti-amyloid treatment and brain stimulation in the 3xTg-AD mouse line by utilizing biochemistry, electrocorticography (ECoG), and mouse behavioral analysis. Mice will be exposed to one of two antibody doses and an rTMS protocol previously shown to improve cognition in 3xTg-AD mice in our laboratory. Treatment conditions for the 3xTg-AD mice include 1) both treatments, 2) one treatment with sham or vehicle, or 3) both sham and vehicle. Wild Type mice (B6) will be included to qualitatively measure stimulation and vehicle sham injection effects. We will assess all mice for a biochemical response (Aim 1), as well as memory and ECoG improvements (Aim 2). To bridge the gap between human and rodent research, we will quantify ECoG and stimulus-evoked responses with the expectation to normalize hyperactivity. ECoG measurements will also double as an assesement for seizure-related activity to test for translatable safety concerns. Results from this proposal will provide valuable insight into combining two therapies, capable of tackling different aspects of MCI and AD. Successful implementation of this research could open the door to a new avenue of treatment for neurodegeneration and result in improvement in the quality of life for many suffering from this disease.
