Intranasal neprilysin rapidly eliminates amyloid-beta plaques, but causes plaque compensations: the explanation why the amyloid-beta cascade may fail?

Neurodegenerative brain disorders are a major burden in our society, such as Alzheimer ' s disease. In order to repair or prevent such diseases, drugs are designed which enter the brain, but the blood-brain barrier limits their entry and the search for alternative pathways is important. Recently, we reported that intranasal delivery of the amyloid-beta degrading enzyme neprilysin eliminated amyloid-beta plaques in transgenic Alzheimer ' s disease mice. This review describes the anatomical structure of the intranasal pathway, explains the intranasal delivery of pure neprilysin, cell-loaded neprilysin (platelets) and collagen-embedded neprilysin to destruct amyloid-beta plaques in Alzheimer ' s disease in transgenic APP_SweDI mice and hypothesizes why this may cause compensation and why the amyloid-beta cascade hypothesis may fail.

Automated summary

Neurodegenerative brain disorders, such as Alzheimer's disease, pose a significant burden on society. Delivery of an amyloid-beta degrading enzyme, neprilysin, through the intranasal pathway has been found to eliminate amyloid-beta plaques in transgenic Alzheimer's disease mice. This method shows promise as an alternative approach for treating Alzheimer's disease.