What Are the Potential Therapeutic Benefits of Targeting Blood-Borne Lipoproteins in the Treatment of Alzheimer’s Disease?

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, the deposition of amyloid-β (Aβ) plaques, the formation of neurofibrillary tangles, and cerebrovascular dysfunction. Evidence suggests that blood-borne lipoproteins play a role in the disease’s pathophysiology by influencing the cerebrovasculature and amyloid metabolism. Low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) can contribute to oxidative stress, endothelial dysfunction, vascular dysfunction, and the accumulation of amyloidogenic peptides, thereby exacerbating neurodegeneration. The role of lipoprotein(a) (Lp(a)) remains unclear, whereas high-density lipoprotein (HDL) is recognized for its cerebroprotective properties, including anti-inflammatory and vasoreactive functions. These properties help to maintain neuronal homeostasis and facilitate the clearance of Aβ from the brain. This review summarizes the current evidence regarding the role of lipoproteins in AD and discusses how therapeutic strategies targeting lipoprotein pathways, such as lipid-lowering agents and HDL mimetics developed for cardiovascular diseases, may benefit patients with AD.