HDL-Apolipoprotein in Alzheimer's Disease Revisited: From Periphery to CNS

High-density lipoprotein (HDL), as a crucial component of lipid metabolism, have roles in regulating Alzheimer's disease (AD) core pathology amyloid β (Aβ) and phosphorylated tau (p-tau) through its apolipoproteins, which are associated with brain structures, cognition, and risk of dementia. The pool of HDL apolipoproteins—in the brain and in the periphery—has its own distinct origin, composition, and regulatory mechanisms. It remains unclear whether these apolipoproteins in the periphery and CNS play distinct roles in the pathogenesis of AD. Specifically, this review focus on the distinct associations of apolipoprotein AI and apolipoprotein E—the major components of HDL in the blood and CSF—with pathological proteins, brain integrity, cognition, and dementia progression in AD. We summarize and examine the current state of knowledge on the values of these apolipoproteins in AD pathogenesis and clinical potential.