Nitric Oxide-Mediated Changes in Glymphatic and CSF Systems in Aging and Alzheimer's Disease

ABSTRACT Here we apply for a research supplement to our R01 grant from the NIA, submitting it in response to PA-21-071 which is directed at fostering diversity in scientific research workforce and developing the careers of eligible investigators. We present a detailed plan to advance the professional career of Kennelia Mellanson, a graduate student in the laboratory. Kennelia’s current project focuses on novel quantitative approaches to determine the key components of the ventricular and glymphatic system of transport in the brain – the ciliary beat, the directional flow of the cerebrospinal fluid (CSF), and the structure of the brain ependymal layer – features that are critical for the efficient ventricular transport of the CSF, and the structure of the aquaporin 4 (AQP4) channels, which serve as the key components of the glymphatic system of transport. Our proposal is in full alignment with the original R01 grant from the NIA “Glymphatic and CSF systems in aging and Alzheimer’s disease”, which focuses on the mechanisms of the brain tissue homeostasis and clearance in Alzheimer's. We now propose using our new techniques and findings on the ventricular and glymphatic transport to determine the changes accompany aging and progression of the Alzheimer's disease in a mouse model and to use this project as a platform for helping and directing Kennelia Mellanson in developing her career as a researcher and a scholar. We present a detailed plan for Kennelia’s professional development, including a detailed plan and timeline for mentorship, manuscript and grant writing, didactic activities, improving the presentation skills, participation in meetings and courses, and networking. Furthermore, we present a research plan for studying the key components of the transport systems that may be compromised by aging and by Alzheimer's disease.