Study of neprilysin gene therapy targeting the glymphatic pathway for the treatment of Alzheimer’s disease

Qiang Liu, Huanxing Su, M.D, Ph.D.


Associate Professor, University of Macau



Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by amyloid-β (Aβ) deposits and neurofibrillary tangles. Currently there are no effective therapies available for the treatment of AD. Despite the failure of many clinical trials that target at reducing Aβ deposits over the past 5 years, it is still believed that Aβ is a promising target for the treatment of AD. Accumulating evidence suggests that Aβ should be cleared away in an efficient and prompt manner at early disease stages. Recent studies have demonstrated a brain-wide pathway along the cerebral vasculature termed as the glymphatic system which facilitates the influx of cerebrospinal fluid into the parenchyma throughout the brain, suggesting that the glymphatic pathway could be a promising drug delivery route for the treatment of brain disorders. The present study investigated whether delivery of neprilysin (NEP), an enzyme that has a potent effect on degrading Aβ, via the glymphatic pathway could efficiently degrade Aβ deposits in extracellular spaces in APP/PS1 AD transgenic mice and eventually lead to cognitive improvement. The results of the study provide evidence that delivery of therapeutic agents via the glymphatic pathway could be a novel approach for the treatment of AD.