Start here: ApoE4 carriers have impaired delivery of omega-3 fats to their brain. Essentially, the brain is genetically deprived of these essential fatty acids, EPA/DHA.
End result: Higher risk of Alzheimer’s disease (AD).
I have outlined in a few other posts the importance of ApoE genetic testing and its relevance to Alzheimer's disease (not to downplay it's role in cardiovascular disease, but both are equally effected and are interchangeable in their role in AD. But if you needed a quick breakdown here it is.
ApoE 2/3 - Lower risk
ApoE 3/3 - Neutral - No increased risk (this is what ApoE3/4 and 4/4 are compared to)
ApoE 3/4 - Higher risk
ApoE 4/4 - Highest risk
A recent study showed that individuals with an ApoE4 allele (3/4 or 4/4) have impaired delivery of omega-3 fatty acids (EPA and DHA - found in fish) to their brain. More specifically lower levels of EPA and DHA in their cerebral spinal fluid (CSF). This essentially means the brains of ApoE4's (people who have an ApoE4 allele - including myself) do not have the are deprived of essential fatty acids, EPA and DHA. Whereas those without an ApoE4 allele had higher levels of EPA and DHA in their CSF, so their brains were bathing in it, while ApoE4 brains were "dry."
When I think of this, I wonder, well if their brain lacked omega-3 fats then what took their place? Omega-6 oils, arachidonic acid, highly oxidized vegetable oils (corn oil, soybean oil, canola oil)?! Researchers didn't check but I suspect an abundance of pro-inflammatory oils misplacing the anti-inflammatory EPA and DHA play a major role. Just a hypothesis.
This is really interesting stuff because we know ApoE4 carriers have higher risk for AD, for multiple reasons - some being cardiovascular, inflammatory, poor glucose utilization (diabetes of the brain) - but now we see that it could be due to lower delivery of essential fatty acids to the brain, especially DHA. This is important because now doctors can (I hope they do) begin using high doses of EPA and DHA for their patients.
Most medical doctors are familiar with pharmaceutical fish oil, one being Vascepa. Which recently has been identified to reduce cardiovascular disease risk significantly. However, it didn't lower cholesterol levels (LDL-C), but thats for another day... My point here is that Vascepa is only EPA, not DHA. It is the DHA that we suspect has the neurocognitive benefits, so a drug won't do the trick for AD prevention - in case you were wondering.
So if you have a family history of Alzheimers, have an ApoE4 gene and DO NOT want to get Alzheimers, I think DHA and EPA is a no-brainer [insert pun here 😉]
Remember you can't get adequate doses of EPA and DHA from plants, since plants make ALA which needs to be converted to EPA and DHA. Instead, I would go straight for the marine sources.
Arellanes IC, Choe N, Solomon V, et al. Brain delivery of supplemental docosahexaenoic acid (DHA): A randomized placebo-controlled clinical trial.EBioMedicine. 2020;59:102883. doi:10.1016/j.ebiom.2020.102883