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

• DOI: 10.1073/pnas.1908658117
• Publication Date: 2020-12-07T21:35:43Z
• Authors: Sonam Dubey; Stefan Heinen; Slavica Krantic; JoAnne McLaurin; Donald R. Branch; Kullervo Hynynen; Isabelle Aubert
• Keywords: 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

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 passage antibodies from blood In a mouse model disease, blood, and without FUS, reduced amyloid pathology. contrast, FUS was required deliver sufficient hippocampus effectively promote neurogenesis. Neurogenesis, regenerative process involved memory functions, impaired disease. Putative contributors stimulation neurogenesis include decrease proinflammatory cytokine TNF-α. holds potential increase for