The reasons underlying these inconsistencies are not clearly understood. Indeed, results obtained with multiple biochemical, histochemical, and ultrastructural methods, mainly performed by Cristina Curcio’s team, suggest that RPE secretes apolipoprotein B lipoprotein particles of unusual composition into BrM, where they accumulate with age eventually forming a lipid wall that is a precursor of basal linear deposit. In addition, an accumulation of oxidized ApoB100 lipoproteins in BrM, drusen and basal deposits have been observed in AMD. In atherosclerosis, the oxidation of ApoB100 lipoproteins lead to mainly innate immune system-mediated inflammation which initiates a cascade of pathological events ending with the formation of atherosclerotic plaques. Thus, the oxidized ApoB100 in BrM have been suggested to initiate inflammation, innate immune response and drusen formation sharing with the ‘‘response to retention’’ hypothesis of Z-VAD(OH)-FMK atherosclerosis. In this hypothesis, the retention of cholesterol-rich, atherogenic lipoproteins provokes a cascade of responses that lead to disease in a previously non-lesional artery. Similarly, it has been suggested that in AMD, the retention of a sub-endothelial apolipoprotein B may lead to the formation of AMD lesion. However, this theory does not exclude the potential contribution of lipoprotein synthesized in the liver or in intestine transported by bloodstream. The increasing number of studies associating high HDL with increased risk for AMD suggests the possibility of a real relationship between high HDL and AMD, which might be due to a dysfunction of HDL. Recent findings on strategies to reduce cardiovascular risk turned attention to HDL quality rather than quantity. Some studies suggested that plasma HDL concentrations do not predict functionality and composition of HDL and may be a potential factor of conflicting results in the literature. Indeed, HDL are highly heterogeneous in structure and biologic function. The anti-oxidant and anti-inflammatory activities of HDL can become ineffective due to inflammation and other factors such as myeloperoxidase-mediated oxidation. Consequently,Z-LEED-FMK HDL may turn into dysfunctional, pro-inflammatory and pro-oxidant particles that promote LDL oxidation and impair cholesterol efflux and reverse cholesterol transport. Thus, recent studies suggested that testing functionality, composition and anti-inflammatory properties of HDL will be better markers than testing plasma HDL concentration for identifying subjects at risk for coronary heart disease. Briefly, HDL subclasses can be classified by their density, their size their charge and their main apolipoprotein content. Under dyslipidaemic conditions, changes in HDL subfraction levels and functions are currently observed. HDL2 and more particularly HDL2b seem to be more predictive of coronary heart disease risk than HDL or HDL3. Accordingly, it has been reported that, HDL2b levels are lower in subjects with coronary artery disease compared to healthy subjects and inversely related to disease severity and progression of coronary lesions. Furthermore, the concentration of pre-bparticles has been found to increase in subjects with coronary artery and heart diseases and with myocardial infarction. Inversely, the levels of large a1- and pre-a particles have been reported to decrease in subjects with coronary heart disease in comparison with healthy subjects.