High-density lipoprotein in Alzheimer's disease: From potential biomarkers to therapeutics

The inverse correlation between high-density lipoprotein (HDL) levels in vivo and the risk of Alzheimer's disease (AD) has become an inspiration for HDL-inspired AD therapy, including plain HDL and various intelligent HDL-based drug delivery systems. In this review, we will focus on the two endogenous HDL subtypes in the central nervous system (CNS), apolipoprotein E-based HDL (apoE-HDL) and apolipoprotein A-I-based HDL (apoA-I-HDL), especially their influence on AD pathophysiology to reveal HDL's potential as biomarkers for risk prediction, and summarize the relevant therapeutic mechanisms to propose possible treatment strategies. We will emphasize the latest advances of HDL as therapeutics (plain HDL and HDL-based drug delivery systems) to discuss the potential for AD therapy and review innovative techniques in the preparation of HDL-based nanoplatforms to provide a basis for the rational design and future development of anti-AD drugs.