E2/E4 Result. How to intrepret this ?

[georgegeorge6565]

Hi guys

My name is George and I did a dna test . Found out I have e2/e4 apo genes.
From my research I understand that e4 is associated more AD and E2 with the lowest.
Having both, do they cancel each other ? I've tried searchinf on the board but haven't found any similar case.
Would really appreciate your insights.

[TheresaB]

Hi guys

My name is George and I did a dna test . Found out I have e2/e4 apo genes.
From my research I understand that e4 is associated more AD and E2 with the lowest.
Having both, do they cancel each other ? I've tried searchinf on the board but haven't found any similar case.
Would really appreciate your insights.

Hi George,

Welcome to ApoE4.info. You are correct, the 2 allele is protective against Alzheimer’s and the 4 allele raises the risk. But put the two together, well, we’re talking genes, not math.

According to this paper, Association of APOE e2 genotype with Alzheimer’s and non-Alzheimer’s neurodegenerative pathologies (Terry E. Goldberg et al, Nature 18 Sep 2020), it appears the 4 is dominant. From the paper's abstract:

The apolipoprotein E (APOE) gene contains both the major common risk variant for late onset Alzheimer’s disease (AD), e4, and the major neuroprotective variant, e2. Here we examine the association of APOE e2 with multiple neurodegenerative pathologies, leveraging the NACC v. 10 database of 1557 brains that included 130 e2 carriers and 679 e4 carriers in order to examine potential neuroprotective effects. For AD-related pathologies of amyloid plaques and Braak stage, e2 had large and highly significant protective effects contrasted with e3/e3 and e4 carriers with odds ratios of about 0.50 for e3 contrasts and 0.10 for e4 contrasts. When we separately examined e2/e4 carriers, risk for AD pathologies was similar to that of e4 carriers, not e2 carriers. For multiple fronto-temporal lobar pathologies and tauopathies, e2 was not significantly associated with pathology. In sum, we found that e2 was associated with large but circumscribed protective effects.

[Laurie Sotro]

Hi guys

My name is George and I did a dna test . Found out I have e2/e4 apo genes.
From my research I understand that e4 is associated more AD and E2 with the lowest.
Having both, do they cancel each other ? I've tried searchinf on the board but haven't found any similar case.
Would really appreciate your insights.

Hello George!

My name is Laurie and as a Support Team Intern, I would like to welcome you to this forum; we are so glad you joined us! You have found a very supportive, informational and encouraging community here.

I can certainly understand that receiving your test results of e2/e4 may initially cause questions such as the one you posed, "Having both, do they cancel each other?" In my understanding they do not. But the good news is, there is so much that you can do to prevent and even "cancel" out any risk factors yourself! And in order to equip yourself to do just that, I can say with certainty that you are in the right place to get started!

I just noticed TheresaB replied to your post previously with some great information! I am sure that was super helpful.

This forum is a wealth of knowledge and encouragement to help support our members.
We invite you take a look around and do a dive deep into this forum.
While you're looking around on this site you will notice just how robust it is with various content and so many amazing areas to check out. I would like to highlight a few areas you might find of interest.

Many of our members find the following links a great place to start since they contain resources to help you become more familiar with our site and receive a solid introduction to all the amazing content we offer.

The How-To Guide includes topics such as navigating the forum, private messaging, and searching. One great tip is to use the quote (") button when replying to a specific post. Using this button will automatically alert that member of your response.

You can browse a wealth of information in both the Wiki and also the Primer , which is a detailed and informative resource written by a practicing M.D. with ApoE4/4.

You may also be interested in learning about other members journeys or even sharing your own story with us, and we welcome you to do so! The encouragement and support found in these stories are some of our members favorite things to read through. If you haven't already checked it out, feel free to take a look with this link:
Our Stories.

Welcome aboard! Please reach out if you have any further questions!

Kindly,
Laurie Sotro
Support Team Intern

[NF52]

Hi guys

My name is George and I did a dna test . Found out I have e2/e4 apo genes.
From my research I understand that e4 is associated more AD and E2 with the lowest.
Having both, do they cancel each other ? I've tried searchinf on the board but haven't found any similar case.
Would really appreciate your insights.

Hi George,

Your combination of ApoE 2 and 4 is not held by nearly as many people as those with ApoE 3/4, who make up about 25% or so of most people with European ancestry. That means it's harder to draw strong conclusions about what any one person's risk is, when only maybe 2-4% of people have ApoE 2/4, and some percentage of those have been in clinical trials where their blood or other biomarkers (PET scans, CSF fluid) and clinical diagnoses can be compared to people like me with ApoE 4/4 or those with ApoE 3/4.

The good news about that is that the evidence is clear that if you avoid diabetes (which some people with ApoE 2 seem to be susceptible to developing) and if you avoid heart disease (a risk for those of us with ApoE 4), you've already done two great things for your brain! We had a member on the forum several years ago who was 84 with ApoE 2/4. She organized meet-ups for others with ApoE 4 in her Seattle neighborhood, lived an active life and kept up with a husband who was at least a decade younger. She only stopped posting when she moved up the coastline to enjoy the ocean life even more.

You didn't mention your age; but you can always practice what one of the Alzheimer's researcher said as a keynote speaker in July: "You're never too young or too old to exercise and eat a healthy diet. What is good your heart is good for your brain and vice versa."

Hope you feel empowered knowing that some day you could help research prove that you have great genes!

Nancy

[Hazelwood]

Hello George from a fellow E2/4. I too have struggled to find much information on this genotype so please share anything you find in your journey. Personally, I have had very good results with keto diet (heavy EVOO), Intermittent fasting (16/8), exercise, focus on sleep and supplements as recommend by Dr. Bredesens book (End of Alzheimer’s). The largest challenge for me appears to be managing inflammation and blood glucose in balance with cholesterol. The results have been remarkable and my memory has actually improved quite a bit over the last five years of this protocol. I have noticed that the B vitamins/ choline / folate need to be supplemented even when showing “normal” levels however that may be individual. Please stay in touch here and thank you again for posting.