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 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.