Generally, plasma concentration of ApoE has been observed as E2 > E3 > E4
That is to say, if you have an ApoE profile of E3/E4 or E4/E4, you are likely to have a lower concentration of ApoE than the people with profiles of E3/E3, E2/3. The very rare E2/E2 having veritable shitloads of the little buggers.
I don't get a lot of time for Pubmed trawling, so when I've spent many hours of running different bait through the search engine, having one paper jump out of the sea with clear and concise observations is rather satisfying. About six months ago I hooked one such paper - Apolipoprotein E serum concentration and polymorphism in six European countries: the ApoEurope Project by Schiele et al in 2000.
The ApoEurope Project being a study of humans from Finland, France, Greece, Northern Ireland, Portugal and Spain.
Which lead me to another - "The importance of plasma apolipoprotein E concentration in addition to its common polymorphism on inter-individual variation in lipid levels: results from Apo Europe" by Haddy et al in 2002.
I'd never heard of the ApoEurope Project, but according to the Schiele paper, the plan is/was to have three parts:
1. epidemiology of Apo E concentration (done)
2. role of Apo E in cardiovascular disease
3. role in Alzheimer's
That I couldn't find any reference at all to parts 2 or 3 in the 14 years since part 1 has me wondering whether they gave up, lost funding or just forgot about it all.
Anyway, back to the point of part one - which is summarised nicely in table 6 of Scheile et al.
As you can see, although there aren't a lot of E2/E2 people to prod with needles, they can have up to around twice the concentration than those of the E4/E4 group.
Scheile's crew also found a relationship between Apo E concentration and age and gender. Concentration being significantly higher in men aged between 25 and 44. After 44, women's concentration increased at a greater rate than the men. Hormones playing silly buggers, I suppose.
The Haddy paper provides not much more except for a lot of rather hysterical comments about cholesterol being on par with cancer and that E4 people are basically screwed as a result.
But ignoring all the nonsense, and there certainly is plenty in the two papers, and Haddy et al did publish some interesting observations regarding triglycerides:
A lot of the papers on ApoE are conflicting or ambiguous regarding triglycerides. Although there didn't seem to be any difference between ApoE phenotypes in Haddy, when they adjusted for ApoE concentration there was:
Or in Haddy et al's words "differences in mean triglycerides between apoE genotypes were much more pronounced when the apoE concentration was considered (Figure 1b). In both sexes, additional correction for the apoE concentration resulted in a decrease in mean triglycerides levels in the presence of the e2 allele and an increase in e4 subjects."
Phew, for a second there I thought being E4/E4 wasn't so bad after all. If I was still eating shedloads of sugar and starches, my 'adjusted triglycerides' would probably be something to behold.
If we remember that E2 isn't that great at binding to LDL receptors, whereas E4 has it down pat, I suppose there's a chance that E4 people are perhaps synthesising as many as they require and no more. E2's have them spewing out because their ApoE appear to have attention deficit and get distracted by all the pretty red stuff floating around.
Or...given that one of the known roles of ApoE is lipid metabolism and also transport of fat soluble vitamins through the body, perhaps the E4 people are sometimes having problems because they don't have as many ApoE to perform this function.
Thinking aloud aside, although our picture of ApoE's role is embarrassingly incomplete, the above relationship does add to the jig-saw puzzle that is being put together.
If you were into making things really simple, you could ignore all the pieces and simply conclude it is cholesterol that is the problem and that lowering it would improve your chances of a healthy brain and heart in retirement. Not as much cholesterol, the ApoE that you have don't need to work as hard.
All those smart people who say E4s should eat a low fat diet seem to follow this logic.
I think they're very wrong, but that's just me.