New member questions

[Girlmom]

Thanks Teresa I’ll check that out. However, I want to quote the 23and me site. I am cutting and pasting from it.
Indications for Use

From the 23andMe website 12/20/19
The 23andMe PGS Genetic Health Risk Report for Late-Onset Alzheimer’s Disease is indicated for reporting of the ε4 variant in the APOE gene. This report describes if a person's genetic result is associated with an increased risk of developing late-onset Alzheimer’s disease, but it does not describe a person's overall risk of developing Alzheimer’s disease. The ε4 variant included in this report is found and has been studied in many ethnicities. Detailed risk estimates have been studied the most in people of European descent.
Special Considerations

This test does not identify or report on the ε2 and ε3 variants of the APOE gene. These variants are not associated with an increased risk of developing Alzheimer's disease.
Genetic testing for late-onset Alzheimer's disease is not currently recommended by any healthcare professional organizations.

So, you can see why this is confusing. While they may collect that DNA, they do not report on it directly and it requires more work to get the 2 and 3. But why do they say 2 and 3 have no association with risk. My question is, does it really matter if I am a 3/4 or 2/4 vs just knowing I am not homo 4?

[TheresaB]

While they may collect that DNA, they do not report on it directly and it requires more work to get the 2 and 3. But why do they say 2 and 3 have no association with risk. My question is, does it really matter if I am a 3/4 or 2/4 vs just knowing I am not homo 4?

Yes, 23andme does collect but doesn't include everything in their report. It was only in the past couple years that the FDA allowed 23andme to even report 4 status. That's why if you run your data through promethease or look up in Snpedia, you can determine your exact status.

2s and 3s can still get Late Onset Alzheimer's but the risk is not elevated as it is with a 4. 2s tend to be lower than 3s, but I understand 2s have other heath concerns such as hypertriglyceridemia. If you read Dr Bredesen's book The End of Alzheimer's he talks about the different types of Alzheimer's and Type 3 Alzheimer's tends to occur more commonly in 3s than 4s. But again, anyone regardless of genotype can get any type of Alzheimer's, such things as diet, exercise, and environmental/toxic exposure play huge roles.

[Girlmom]

So now that I know I have at least inheritors one 4 allele from one of my parents, does this mean with certainty that 1 of my parents at a minimum has at least 1 apoe4 allele? I am 51, with extremely active parents with no cognitive decline, in their late 70’s. I guess the question is asking them if they were at risk, would they want to know? And then, what about my own children? This raises so many questions for me. I will tell them I have the gene and leave the decision up to them.

[NF52]

So now that I know I have at least inheritors one 4 allele from one of my parents, does this mean with certainty that 1 of my parents at a minimum has at least 1 apoe4 allele? I am 51, with extremely active parents with no cognitive decline, in their late 70’s. I guess the question is asking them if they were at risk, would they want to know? And then, what about my own children? This raises so many questions for me. I will tell them I have the gene and leave the decision up to them.

Hi Girlmom!
Since about 75% of people have at least one ApoE 3, about 20% have one ApoE 4 and about 5% have one ApoE 2 (this is approximately the average for people with European ancestry), it's probably safe to assume you are ApoE 3/4, if you don't want to know for sure whether that second allele is a 3 or a 2. So since we inherit one from each parent, your conclusion is exactly right: at least one of your biological parents has a least one ApoE 4.

Here are the combinations that might have led you to be an ApoE 3/4:
Mom: Apoe 3/4, Dad Apoe 3/3
Mom Apoe 4/4, Dad, Apoe 3/3
Mom ApoE 4/4; Dad ApoE 3/4
Mom ApoE 2/4; Dad; ApoE 3/3. And then reverse those for Dad and Mom.
I may have missed a combination possibility, but the fact that your parents are in their late 70's and doing so well proves what we try to repeat often: Genes are not destiny! Scientists now understand that possibly hundreds of genes exert protective effects against ApoE4, while others may add slightly to a risk.

Your parents are roughly in the same age group as I am at age 66. A 2017 meta-analysis of four large cohorts of people, most of them followed for decades, came up with the following prediction of the risk of a diagnosis of EITHER mild cognitive impairment (MCI) or dementia by the age of 85, for people currently ages 60-75 with ApoE 3/4:

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)...The regression models are insufficiently precise for “personalized medicine” incidence estimates based on sex, education, or other factors, but they do allow for qualitative adjustments to overall stratified risk estimates.

APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts

So it's wonderful, but not surprising that they are both doing well. Assuming that only one parent has ApoE 3/4, that parent has only a 20-25% chance of getting either Mild Cognitive Impairment or Alzheimer's by age 85; the other has only a 10-15% chance of that. Some studies of age at diagnosis suggest that people who have made it to their late 70's with ApoE 4, without MCI or AD, have only about the same risk as their ApoE 3/3 friends--in other words, at that age the risk is based on age, not genes.

You may want to read this thread before talking to them or your children, and to think about what you know about their reactions to uncertain health risks Thinking About Testing

Best wishes for finding this journey into unexpected territory one that makes you feel more empowered and more confident of your family's healthy future.