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Abstract #2022

Investigating Glumphatic Function During Early Tau Pathology Using Dynamic Contrast-Enhanced MRI

Ozama Ismail1, Ian F Harrison1, Jack A Wells1, Yolanda Ohene1, Payam Nahavandi1, Alexander V Gourine2, Zeshan Ahmed3, Alice Fisher3, Tracey K Murray3, Ross A Johnson4, Emily C Collins4, Michael J O'Neill3, and Mark F Lythgoe1

1UCL Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom, 2Neuroscience, Physiology & Pharmacology, University College London, London, United Kingdom, 3Eli Lilly & Company, Surrey, United Kingdom, 4Eli Lilly & Company, Indianapolis, IN, United States

Pathological accumulation of tau and amyloid in the brains of Alzheimer’s disease (AD) patients leads to a continuum of irreversible biochemical and pathological changes and pronounced neurodegeneration. Impaired ‘glymphatic’ clearance may be one of the earliest biological changes in AD, occurring many years prior to neurodegeneration, and therefore presents a unique opportunity for strategic therapeutic intervention. Here, we have mapped the extent of glymphatic inflow of an MRI contrast agent from cerebrospinal fluid, into the brain parenchyma. Leading on from previous studies, we have demonstrated that glymphatic inflow is impaired during the onset of pathology in an AD animal model.

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