We measured the concentration of apolipoprotein E (apoE) in plasma from 184 non-fasted subjects in order to determine whether important variations might exist linking plasma apoE levels to clinical phenotypes among early and late onset sporadic Alzheimer's disease (AD) and Down's syndrome (DS). A significant increase in the level of plasma apoE was observed in non-fasted late-onset AD patients (with a mean level of 3.26 +/- 0.08 microgram apoE/mg total protein for n = 84 patients) when compared with the plasma apoE levels of control individuals (mean of 2.32 +/- 0.10 microgram apoE/mg total protein, n = 51 patients; P < 0.001). A similar increase was found for non-fasted early-onset AD patients (mean of 3.69 +/- 0.17 microgram apoE/mg total protein, n = 20) when compared with the plasma apoE levels of control individuals (P < 0.001). Plasma apoE levels for DS patients did not differ significantly from those of controls (P > 0.05). The association of elevated plasma apoE levels in AD may be relevant to clarifying the mechanism(s) whereby apoE isoforms specify differential risk for development of AD.