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

摘要

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.