Virginia Research Day 2021

Medical Student Research Cl inical

05 Novel MRI Techniques Identifying Vascular Leak and Paravascular Flow Reduction in Early Alzheimer Disease

McNichols, Courtney; Hall, Colton; Orciuolo, Jason; Young, Amelia; Trenton, Judd; Daugherty, Daniel; Joseph, Charles, MD Corresponding author: cmmcnichols@liberty.edu

Liberty College of Osteopathic Medicine

With beta-amyloid (Aß) and Hp-tau (Hpt) antibody treatment trial failures, avenues directed to other facets of Alzheimer’s Disease (AD) pathophysiology are being explored to treat in the preclinical or early clinical state. Previous studies of the early AD process have established evidence of blood brain barrier (BBB) breakdown and impaired glymphatic (paravascular and interstitial) fluid waste clearance. These two dysfunctions, as components of AD, are reasonable candidates to explore for future treatments in high-risk patients. Ideally, human treatment trials require non or minimally invasive tools for quantifying improvements in BBB integrity and glymphatic fluid clearance, correlating with clinical outcomes. Since AD treatment trials require pathologic confirmation for diagnosis, established serologic, cerebral spinal fluid (CSF), and imaging biomarkers are utilized. Future treatment trials in longitudinal studies demand additional biomarkers to identify BBB leak and glymphatic flow reduction combined with existing pathologic and clinical biomarkers to assess results. Novel candidates for identifying BBB leak and delayed glymphatic clearance are high resolution dynamic contrast imaging (DCI) and non-invasive 3D pulsed arterial spin labeling (PASL) MRI.

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