The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 13 No.
3 • June 2010
Alzheimer’s Disease and ApoE4
ApoE4 Found to be Carried by VLDL and Is Possibly
Converted by VLDL Into a More Pathogenic Form
An interesting 2010 paper reports that “after every meal, VLDL fluidity is increased causing apoE4 associated with VLDL to assume a more expanded conformation, potentially enhancing the pathogenicity of apoE4 in vascular tissue.” The researchers found that “[l]ike the native apoE proteins, spin-labeled apoE4 preferentially associated with VLDL and apoE3-like protein with HDL after a moderately high-fat meal.”
As the authors explain, apoE4 is pro-inflammatory and associated with increased risks of both atherosclerosis and Alzheimer’s disease. Following a meal, there is a state of increased lipolysis (fat breakdown into fatty acids). “During lipolysis, fatty acids accumulate at the lipoprotein surface because the rate of fatty acid transfer is much slower than lipolysis.” The result is an accumulation of fatty acids on the lipoprotein surface that could mediate changes in lipoprotein fluidity. Indeed, as postprandial increases in lipid levels have been “implicated in the development of atherosclerosis via repetitive injury to the arterial endothelium,” the authors suggest that it is important to understand how changes in lipoprotein fluidity resulting from an accumulation of fatty acids might affect apoE isoforms and their conformation in modulating proinflammatory processes important in atherosclerosis.
The authors find that apoE4 assumes a more linear conformation on VLDL particles as a result of increased fatty acids in VLDL due to lipolysis and that the increase in free fatty acid content is accompanied by an increase in lipid fluidity. They suggest that the dramatically changed conformation of apoE4 in postprandial VLDL may be associated with the contribution of apoE4 to atherosclerosis, but that further research will be needed to determine whether this is the case.
If the hypothesis that altered conformation of apoE4 associated with VLDL is associated with greater apoE4 pathogenicity in vascular tissues is correct, it may be useful for that reason alone to keep VLDL levels low. Fortunately, niacin very effectively reduces lipolysis as well as LDL, VLDL, and triglyceride levels. We both take 12 capsules a day of our Niacin Easy 200™ capsules (2.4 grams of niacin a day). It is important to remember that doses of niacin greater than 800 mg a day can, in some sensitive individuals, cause liver damage. If you wish to take higher doses than that, you will need to have yourself tested regularly for liver enzyme levels (as we do) to detect any possible liver damage as a result of high dose niacin which, when detected early, quickly returns to normal when niacin is discontinued.
- Tetali et al. VLDL lipolysis products increase VLDL fluidity and convert apolipoprotein E4 into a more expanded conformation. J Lipid Res 51(6):1273-1283 (2010).