Clinically approved IVIg delivered to the hippocampus with focused ultrasound promotes neurogenesis in a model of Alzheimer’s disease

Male 0301 basic medicine Neurogenesis Biological Availability Mice, Transgenic Plaque, Amyloid blood–brain barrier Hippocampus 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Alzheimer Disease intravenous immunoglobulin Animals Humans Ultrasonics [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] 14. Life underwater Microbubbles Tumor Necrosis Factor-alpha Immunoglobulins, Intravenous MRI-guided focused ultrasound Magnetic Resonance Imaging 3. Good health neurogenesis Disease Models, Animal Treatment Outcome Blood-Brain Barrier Female immunotherapy Central Nervous System Agents
DOI: 10.1073/pnas.1908658117 Publication Date: 2020-12-07T21:35:43Z
ABSTRACT
Significance The efficacy of immunotherapy in Alzheimer’s disease is limited, partly because antibodies, administered peripherally, have poor access to the brain. Focused ultrasound (FUS) with microbubbles allows the passage of antibodies from the blood to the brain. In a mouse model of Alzheimer’s disease, antibodies administered in the blood, with and without FUS, reduced amyloid pathology. In contrast, FUS was required to deliver sufficient antibodies to the hippocampus and effectively promote neurogenesis. Neurogenesis, a regenerative process involved in memory functions, is impaired in Alzheimer’s disease. Putative contributors to the stimulation of neurogenesis include a decrease in the proinflammatory cytokine TNF-α. FUS holds potential to increase the efficacy of immunotherapy for Alzheimer’s disease.
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