A B S T R A C T A radioimnmnoassay for apolipoprotein E in huiman blood serum has been developed that measures equally the major polymorphic species of the protein (apolipoproteins E-1, E-2, E-3, and E-4) and the apo E in the dimer of apolipoproteins E and A-II. The assay is specific and yields values for apolipoprotein E in very low density lipoproteins that agree closely with those obtained by a quantitative electrophoretic method.Apolipoprotein E is also present in at least one species of high density lipoprotein, but the content of apolipoprotein E in the lipoprotein fractions of plasma is uncertain owing to dissociation during ultracentrifugation. The concentration of apolipoprotein E is higher in serum of normolipidemic, premenopausal women than in men of comparable age and is a direct function of the serum triglyceride level. Apolipoprotein E levels are increased out of proportion to triglyceride levels in hyperlipidemic patients with familial dysbetalipoproteinemia (homozygotes for lack of apolipoprotein E-3). Heterozygous relatives of homozygotes have significantly higher apolipoprotein E levels in serum than unaffected relatives. The concentration of partially degraded (remnant) triglyceride-rich lipoproteins also appears to be increased in heterozygotes, who comprise about 15% of the population.

We used the low molecular weight form of apolipoprotein B (B-48) as a marker for the identification of remnant particles formed from chyiomicrons in the plasma of patients with familial dysbetalipoproteinemia. In the serum of patients fasted 14 hours, the d < 1.006 g/cm 3 lipoproteins of prebeta mobility, separated by starch block electrophoresis, contained only the primary hepatogenous species of apolipoprotein B (B-100), and their llpld composition resembled that of normal prebeta very low density lipoproteins. In contrast, the fraction with beta mobility contained both the B-48 and B-100 proteins; the B-48 protein was found primarily among the largest particles. All fractions of beta mobility were greatly enriched with choiesteryi esters. The beta fraction thus contains remnant particles which appear to originate both from chyiomicrons and hepatogenous very low density lipoproteins. It appears that these remnant particles share a common removal mechanism which is impaired in familial dysbetalipoproteinemia. (Arteriosclerosis 3:47-56, January/February 1983) amilial dysbetalipoproteinemia (F. dys.) (type III hyperlipoproteinemia) is now recognized as a disorder in which remnant-like particles, formed from triglyceride-rich lipoproteins, accumulate in plasma.12 Clinically, it is associated with arteriosclerosis of both the coronary and peripheral circulations. 3These remnant-like lipoprotein particles are enriched with choiesteryi esters 1 2 ' 4 and have beta mobility upon electrophoresis in agarose gel, in contrast with normal very low density lipoproteins (VLDL), which have prebeta mobility. The electrophoretic mobility of remnant particles is accounted for principally by deficiency of the C-apoproteins, which are normally the preponderant species in VLDL, with retention of appreciable quantities of less anionic apolipoprotein E (apo E). 5 The initial stages of intravascular lipolysis appear to proceed relatively normally. Removal of remnant particles from the plasma normally occurs rapidly by means of receptor-mediated endocytosis in the liver.2 In F. dys., however, there is