Apolipoprotein (Apo) E4 is a key genetic risk factor for Alzheimer’s disease (AD). In the central nervous system, ApoE-containing high-density lipoprotein (HDL)-like particles transport glial cholesterol to neurons, playing a crucial role in neuronal membrane remodeling and maintenance of the myelin sheath. Despite this, the impact of HDL-like cholesterol trafficking on AD pathogenesis is not yet fully understood.The objective was to examine cholesterol transport via HDL-like particles in cerebrospinal fluid (CSF) of AD patients compared to control individuals. Additionally, we explored the ability of ApoE4-containing HDL to regulate the cholesterol efflux pathway in astrocytoma cells and facilitate cholesterol delivery to neurons.Mass spectrometry (MS) was used for a detailed analysis of the HDL-like proteome in AD patients and controls.