Concentration and distribution of human plasma apolipoprotein E.

(1) A sensitive, specific radioimmunoassay for human apolipoprotein E is described. (2) The method gave a plasma apolipoprotein E concentration of 0.107 +/- 0.051 g/l n = 55) in normal subjects. This value increased significantly (to 0.179 +/- 0.088 g/l) in type II hyperlipoproteinaemia (n = 31, p less than 0.01). Type III subjects formed a distinct group whose mean plasma apolipoprotein E concentration was increased four fold over normal (p less than 0.001). The level in type IV subjects (0.136 +/- 0.056, n = 30) did not differ significantly from the normal value. (3) When plasma was subjected to gel filtration on columns of 6% agarose, apolipoprotein E was located in three regions. Peak I corresponded to very low density lipoproteins, Peak II to the area between very low density and low density lipoproteins and Peak III to the leading edge of the high density lipoprotein fraction. No E protein eluted from the column after high density lipoproteins. (4) In contrast, ultracentrifugation of plasma resulted in up to 40% of apolipoprotein E appearing in the lipoprotein-free (d greater than 1.21 kg/l) fraction. This protein appears to hae been stripped largely from high density lipoprotein during ultracentrifugation. (5) Compositional analysis of very low density, intermediate density and low density lipoproteins isolated by a cumulative flotation procedure showed that the apoE/apoB ratio was the same in the first two species but fell to a very low value in low density lipoproteins.