VPS35 and Alzheimer disease: Whereas, these observations support the view for loss of the Vps35 function to contribute to the AD development, and the increase of the neuronal Vps35 expression at the neonatal age could attenuate AD-relevant pathology in the aged 3xTg-AD mouse model, the details of Vps35 therapy (e.g., dose, critical time window, and key brain regions that AAV-Vps35 are expressed) and the underlying mechanisms of the Vps35 function remain elusive.