**9. Apolipoproteins**

366 Lipoproteins – Role in Health and Diseases

the retina, and are consistent with our findings.[60;64]

In 2007, Connor *et al* reported on the role that HDL plays in the transport of L and Z in serum in a study involving WHAM chicks.[64] WHAM chickens have a recessive sex-linked mutation in the *ABCA1* transporter gene that results in very low circulating HDL concentration, with normal, or increased, concentrations of other plasma lipoproteins, particularly LDL. The analogous mutation in humans results in Tangier disease, which is characterized by a similar deficiency in circulating HDL concentration.[72] In their study, involving 24 WHAM chicks and 24 control chicks, Connor *et al* found that one-day old WHAM chicks had only 9% of the L concentration in plasma when compared with control chicks, and only 6% of the retinal concentration of controls (the corresponding concentrations of Z were 6% and 9%, respectively). Following a high-L diet for 28 days, there was a significant increase in the plasma and retinal concentrations of L in WHAM chicks and controls, but the increases were still greatly inferior in the WHAM chicks when compared with control chicks and, furthermore, still did not reach the concentrations observed in the one-day old control chicks. The observations of Connor *et al* suggest an important role for HDL in the transport of L and Z in serum and/or their incorporation into

Interestingly, although all subjects in our study were healthy volunteers with no evidence of ocular pathology, it is notable that, on average, subjects with a positive family history of AMD had a higher serum concentration of L than subjects with a negative family history of AMD, yet MP optical density levels in both groups were comparable, as were serum concentrations of HDL.[60] As was shown in this study, and as has previously been documented,[73] serum concentrations of L and Z generally correlate positively with MP optical density. Therefore, it is plausible to suggest that in the subjects in this study with a positive family history of AMD, the delivery to, and/or uptake by, the retina of the macular carotenoids is defective when compared to subjects without such a family history.[60] Indeed, although MP optical density levels were comparable between subjects with and without a family history of AMD, subjects with a positive family history of this disease also had higher serum L concentrations. This is consistent with the observations of Nolan *et al*, where a relative lack of MP was seen in association with a positive family history of AMD in 828 healthy subjects, but where dietary and serum concentrations of L and Z were comparable for subjects with and without a family history of this condition, suggesting defective retinal capture of circulating L and/or Z in persons who are genetically predisposed to AMD.[31] Mechanisms governing the retinal capture and/or stabilization of L and/or Z may be subject to influence by HDL subspecies profile, by affecting receptormediated uptake of these carotenoids from serum. Indeed, apolipoprotein profile is probably a determinant of retinal uptake of the macular carotenoids from serum, reflected in our recently reported finding that individuals with at least one Apo ε4 allele exhibit significantly higher MP optical density than individuals without this protective allele, despite statistically comparable serum concentrations of L and Z.[74] Interestingly, the lack of an association between MP optical density and either serum cholesterol concentration or serum HDL concentration in our study would suggest that our observations are more likely due to impaired uptake and/or stabilization of circulating L and/or Z by the macula than Plasma lipoproteins include one or more protein constituents, known as apolipoproteins. Apolipoproteins have been classified into several subgroups, including apolipoprotein A (ApoA), apolipoprotein B (ApoB), apolipoprotein C (ApoC), and apolipoprotein E (ApoE). These subgroups are themselves further sub-classified, for example: ApoA-I, ApoA-II etc. Each lipoprotein class is associated with certain apolipoproteins, for example: chylomicrons and VLDL are associated with ApoB; chylomicrons, VLDL and HDL are associated with ApoE.[76] The primary role of apolipoproteins is the transport and redistribution of lipids amongst various tissues in the body. Specific apolipoproteins are recognised by cell surface receptors, and this facilitates the high affinity binding required for delivery to target tissues. Certain apolipoproteins also act as cofactors of enzymes involved in lipoprotein metabolic pathways, including those of lipoprotein lipase and lecithin-cholesterol acyl transferase (LCAT), which catalyse the formation of cholesterol esters. Another role of specific apolipoproteins is the maintenance of the structure of lipoproteins, by stabilizing their micellar structure, and by providing a hydrophilic surface in association with phospholipids.[53] The function of apolipoproteins has provoked interest in their possible role in a range of degenerative conditions. In particular, several investigators have suggested an association between ApoE and various diseases, including Alzheimer's disease, atherosclerosis and AMD.[77-80]

Abalain *et al.* investigated the association between AMD and serum levels of lipoproteins and lipoparticles.[78] They found that there was no difference in serum ApoA-I and ApoB levels between AMD patients and controls. However, they found that serum ApoE levels were higher, and that serum ApoC-III levels were lower, in AMD patients compared with controls. The higher level of serum ApoE in AMD patients is consistent with the findings of Boerwinkle and Utermann, who found that the Apo ε4 allele is associated with lower serum ApoE levels, and that the Apo ε2 allele is associated with higher serum levels of ApoE.[79] ApoC-III interferes with lipoprotein metabolism and, when associated with ApoB as a lipoparticle, it has been shown to be involved in atherogenesis.[80] Abalain *et al.* found no difference in the levels of this particular lipoparticle between AMD patients and controls.[78] The evidence to date suggests that, of the apolipoproteins, ApoE has the strongest association with AMD.
