Alzheimer’s disease (AD) is pathologically characterized by extracellular beta-amyloid (Aβ) plaques and intraneuronal tau tangles in the brain. A therapeutic strategy aims to prevent or clear these Aβ plaques and the Aβ-degrading enzyme neprilysin is a potent drug to degrade plaques. The major challenge is to deliver bioactive neprilysin into the brain via the blood-brain barrier. The aim of the present study is to explore if intranasal delivery of neprilysin can eliminate plaques in a transgenic AD mouse model (APP_SweDI). We will test if collagen or platelets are useful vehicles to deliver neprilysin into the brain. Using organotypic brain slices from adult transgenic APP_SweDI mice, we show that neprilysin alone or loaded in collagen hydrogels or in platelets cleared cortical plaques. Intransasal delivery of neprilysin alone increased small Aβ depositions in the middle and caudal cortex in transgenic mice. Platelets loaded with neprilysin cleared plaques in the frontal cortex after intranasal application. Intranasal delivery of collagen-loaded neprilysin was very potent to clear plaques especially in the middle and caudal parts of the cortex. Our data support that the Aβ degrading enzyme neprilysin delivered to the mouse brain can clear Aβ plaques and intranasal delivery (especially with collagen as a vehicle) is a fast and easy application. However, it must be considered that intranasal neprilysin may also activate more plaque production in the transgenic mouse brain as a side effect.
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Dr. David Lowemann, M.Sc, Ph.D., is a co-founder of the Institute for the Future of Human Potential, where he leads the charge in pioneering Self-Enhancement Science for the Success of Society. With a keen interest in exploring the untapped potential of the human mind, Dr. Lowemann has dedicated his career to pushing the boundaries of human capabilities and understanding.
Armed with a Master of Science degree and a Ph.D. in his field, Dr. Lowemann has consistently been at the forefront of research and innovation, delving into ways to optimize human performance, cognition, and overall well-being. His work at the Institute revolves around a profound commitment to harnessing cutting-edge science and technology to help individuals lead more fulfilling and intelligent lives.
Dr. Lowemann’s influence extends to the educational platform BetterSmarter.me, where he shares his insights, findings, and personal development strategies with a broader audience. His ongoing mission is shaping the way we perceive and leverage the vast capacities of the human mind, offering invaluable contributions to society’s overall success and collective well-being.