APOE4 and Alzheimer’s disease

In yesterday’s post about the association between cataracts and dementia, one of the variables that they solved for was the E4 allele of the apolipoprotein E gene (APOE4).

The E4 allele of the apolipoprotein E gene (APOE) has been firmly established as a genetic risk factor for many diseases including cardiovascular diseases and Alzheimer’s disease (AD)…

Now, you may be wondering why I am writing about this since it technically has very little to do with the eyes. Hear me out. APOE is involved with lipid transport into and out of cells in the body. Poorly controlled lipids can lead to metabolic syndrome which can lead to type 2 diabetes. What happens with diabetes? That’s right, changes in the eyes.

The APOE4 genotype is the primary genetic risk factor for late-onset AD, is associated with cardiovascular diseases, increases risk for metabolic syndrome, and is linked with decreased lifespan.

See, we got there.

Anyway, I have to admit that reading this, I could mostly understand what was going on. However, this was a 300-level stuff looked at with my 100-level understanding of the topic.

The study APOE4 Disrupts Intracellular Lipid Homeostasis in Human iPSC-derived Glia in the March 2021 issue of Science Translation Medicine uses yeast cells to look at APOE4. There is lots of detail in this paper. However, here are the primary things I took from it.

…human glia with an APOE4 genotype accumulate unsaturated triglycerides leading to a lipid imbalance…

This lipid imbalance found in the glial cells is thought to lead to earlier onset AD. Specifically, free triacylglycerides are stored in the cytoplasm of cells and are called lipid droplets.

…microglia, which play a key role in AD and were recently described to accumulate lipids in aged mice…

Following 2 weeks of culture in minimal media, APOE4 microglia displayed a trend towards increased lipid droplet numbers per cell when compared to APOE3 microglia.

They did find a mechanism to blunt the effects of the APOE4 gene.

…choline supplementation decreased both intracellular triacylglycerides and the quantities of unsaturated fatty acids attached to triacylglycerides in APOE4-expressing yeast to levels found in APOE3-expressing cells. In line with this result, choline supplementation also prevented lipid droplet accumulation in APOE4-expressing yeast…

I would never go so far as to recommending supplements. However, this is something to keep an eye on. APOE4 seems to play a role in a lot of issues with people as we age. Having a relatively simple way to keep this in check might make the aging process much easier. Plus, think of all the meds that patients could stop taking. Wild stuff.