Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide and its incidence is increasing due to the ageing population. Currently, the main limitations of AD treatment are low blood-brain barrier permeability, severe off-target of drugs, and immune abnormality. In this review, four hypotheses for Alzheimer's pathogenesis and three challenges for Alzheimer's drug delivery are discussed. In addition, this article summarises the different strategies of brain targeting nano-drug delivery systems (NDDSs) developed in the last 10 years. These strategies include receptor-mediated (transferrin receptor, low-density lipoprotein receptor-related protein, lactoferrin receptor, etc.), adsorption-mediated (cationic, alkaline polypeptide, cell-penetrating peptides, etc.), and transporter-mediated (P-gp, GLUT1, etc.). Moreover, it provides insights into novel strategies used in AD, such as exosomes, virus-like particles, and cell membrane coating particles. Hence, this review will help researchers to understand the current progress in the field of NDDSs for the central nervous system and find new directions for AD therapy.HighlightsCharacteristics and challenges based on the pathogenesis of AD were discussed.Recent advances in novel brain-targeting NDDSs for AD over the past 10 years were summarised.
Keywords: Alzheimer’s disease; brain targeting; high off-target rate; immune abnormality; nano-drug delivery system.