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
AUTHORS (7)
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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