I need help with my 23andme report...

[NF52]

Is there any effective difference between a 4/2, and a 2/4?

Welcome, Roguejim!
Looks like you've already discovered what a helpful, knowledgeable site this is, and had at least a few questions answered. Most references to the two ApoE alleles (which is the term for alternative forms of a gene that have occurred in the past by mutation and continue to be found in human DNA) are simply put in numerical order. So someone will say "I am a 2/4, or a 2/3, or 3/3, or a 3/4 or 4/4". The scientific term is either heterozygous or homozygous. My husband is a homozygous ApoE 3/3; I am a homozygous ApoE 4/4. Our three children could only inherit a "3" from him and a "4" from me, so we know they are heterozygous ApoE 3/4.

We also know that while having Apoe 4 is associated with an increased risk of Alzheimer's disease (AD) and possible other dementias such as vascular dementia due to cardiac risks, people with ApoE 3/3 can also develop AD and other dementia.

It seems that ApoE 2 may provide some protection against the risk of ApoE 4, although the reasons are not yet well-understood. Here's an exciting finding from a large meta-analysis of 6 populatio-based studies in Europe, just published two weeks ago!

Compared with homozygous APOE-ε3 carriers, APOE-ε2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P = 1.1*10-2) Compared with APOE-ε3, APOE-ε2 is associated with prolonged survival, whereas mortality risk is increased for APOE-ε4 carriers. Further collaborative efforts are needed to unravel the role of APOE and in particular APOE-ε2 in health and disease.

The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE).

Here's another interpretation of the data, from 2017. They provided people ages 60-75 who were screened for a prevention study with this risk prediction of either Mild Cognitive Impairment (MCI) or dementia by the age of 85, the current U.S. expected lifespan for someone 60-75:

The Generation Study elected to disclose the following “lifetime” risks of MCI or dementia to its potential participants: 30%–55% for individuals with APOE-e4/e4; 20%–25% for individuals with APOE-e3/e4 and -e2/e4 (with a note that risk might be lower for those with APOE-e2/e4); and 10%–15% for individuals with APOE-e3/e3, -e3/e2, and -e2/e2 (with a note that risk might be lower for those with APOE-e2/e3 and -e2/e2).

APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts
And with apologies for the length, I'm copying a reply I made to another lucky ApoE2/4 in March, which means all the folks quoted below will now also get an email notifying them of a new member of their exclusive club!

Here's a quick link to a discussion on ApoE 2 from several other ApoE 2/4's, some of whom I've quoted, so they'll know you're in their "club"! New Member - APOE 2/4

My name is Linda and with my doctor's help, I have found out that I am APOE 2/4. With all the research I have done, I am having a hard time seeing any for my type. I am trying to see if I should read and follow the Plant Paradox or should I follow another plan?

I am also APOE4/2, 64 years old, and since we are somewhat rare, there appears to be little specific information that applies just to us. I am following low carb diet- doing the best I can, taking some supplements. I have no cognitive issues, but my family history is very strong for AD. I am not sure what else I need to be doing.

I am also a 2/4. My searching has led me to conflicting information, probably because we are too rare to study. It seems that the keto 12/3 is best. My triglycerides cut in half and my HDL went up. LDLc went up but small particle size isn't too bad. I suggest Calcium CT scoring. Mine was a little high in 2017 so I will retest in another year or so since it's a lot of radiation.

I'm also 2/4, and just joined. Like you, I am finding it hard to pin down what is best for my type.

And here's a quote about ApoE 2's benefit, from a 2016 article: [The bold, and colors are added by me to explain a few terms.]

ApoE2 is relatively rare, with only 5% incidence, and is considered to be a protective variant against AD...Comparatively few studies have explored the role of ApoE2 in relation to AD; yet, overall, the results of these studies suggest that ApoE2 is neuroprotective. AD patients that carry ApoE2 are found to exhibit significantly reduced Aβ [amyloid beta plaques]...(Nagy et al., 1995). In addition, ApoE2-expressing AD brains appear to express less NFT [neurofibrillary tau tangles] formation (Morris et al., 1995), although other studies demonstrate the opposite outcome (Berlau et al., 2009). These conflicting observations of the influence of ApoE2 on pathological manifestation in AD could be explained, in part, by the age difference of the test subjects in the studies... ApoE2 has also been positively associated with cognitive functions in aging. An 8-year-long follow-up study in a large cohort of elderly, dementia-free subjects demonstrated that individuals who possess at least one ApoE ε2 allele (ε2/2 and ε2/3) exhibit improved episodic memory performance...[and] results from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study revealed that ApoE2 carriers have larger hippocampal volume and reduced hippocampal atrophy rate compared to the noncarriers (Chiang et al., 2010). Collectively, these findings suggest that ApoE2 may play a positive role in preserving the structural integrity of the brain, which could account for its cognition-favoring properties in aging brains as well as for the increased resistance to pathological development in early-stage AD brains.

ApoE2 and Alzheimer's disease: time to take a closer look

Be well; your parents both gave you gifts (ApoE 4 also gives the gift of good executive functioning and memory for many years!)

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Take your time to browse, to absorb and to decide what makes sense for you to do with this new information. We'll be here to support you!

[Roguejim]

Thank you for all your help! I am a 61 year old male who has been on keto for about a year. I'm also a LMHR(Lean Mass Hyper Responder). I resistance train 3 days a week, 90 mins per session. My very recent CAC score was 14.4, so, pretty good thus far. I'm also implementing the Pauling Protocol(actually have been for years) for the reduction of atherosclerotic plaque, along with Vit K2 supplementation, et al. I've seen recently that Dave Feldman, a 3/4, is not concerned with saturated fat intake. He is apparently unimpressed with the research/evidence. I'm too new at all this to have an opinion. Still researching...