Hi! I'm new, and have ApoE questions

Newcomer introductions, personal anecdotes, caregiver issues, lab results, and n=1 experimentation.
Lynne
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Re: Hi! I'm new, and have ApoE questions

Postby Lynne » Sat Feb 23, 2019 12:35 pm

mike wrote:
Lynne wrote:I'm wondering how common it is to have Alzheimer's with E3/E3 like my mother? And since her E3's are not really neutral, is it like I have two E4's, since I got my "E3" from her?

Lynne, as was already mentioned, your mom's E3 is neutral, but not all Dementia/AD is caused by ApoE4. Often it can be caused by nutrition deficits in the brain. It looks like mitochondrial problems can also cause dementia. And mitochondrial DNA actually comes down only from your mom. One good way to add nutrition to the brain is to start a keto diet. It might still work for your mom. I'm glad you like science - this is a VERY active field right now, and this website is a great place to start learning. I also found both the Primer and the Wiki to be fantastic resources. Also, use the magnifying glass at top right to search for things like "mitochondria" to learn more. And ask questions.


Thanks for the tips! That magnifying glass search feature will come in very handy, and I love the extensive Primer and Wiki. And thanks for the info on mitochondrial problems, I didn't know about that, this is all very new to me. I may try the Keto diet, I am vegan, so it would be a little harder, but is still doable. :)

Lynne
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Re: Hi! I'm new, and have ApoE questions

Postby Lynne » Sat Feb 23, 2019 12:53 pm

NF52 wrote: People with ApoE 3/3 can and do still get Alzheimer's. I was at a meeting of scientists rating applications for funding for Alzheimer's research in December and they said: The biggest risk factor for Alzheimer's overall is advanced old age. Currently about 1/3 of people over the age of 85 would be likely to get a diagnosis of either Mild Cognitive Impairment (MCI) or Alzheimer's disease (AD), according to a summary of the 2018 international Alzheimer's Association conference. That's actually an improvement over previous decades, when about 50% of people over 85 had AD. If your mother and her parents and brothers developed dementia in their late 70's or 80's, it's possible that it was from a combination of risk factors (including pollution and dietary habits that you don't have).

It's also the case that "Alzheimer's" has become something of a catch-all diagnosis. My own mother was given that diagnosis shortly before she died, after years of slowly worsening memory issues, and a much earlier MRI that showed white matter disease. It's likely that she actually had primarily vascular dementia from years of uncontrolled high blood pressure with some AD pathology in addition. Her own mother died of a stroke at age 45, another indication of vascular issues.


Thanks for the confirmation that people with E3/E3 can still have Alzheimer's. When I first got my mother's results, I thought it wasn't possible, and I got 23andMe to re-run her sample. They didn't want to do it, but I persisted and they finally did it for me. If I had known then what I know now, I wouldn't have bothered them!

My mother's neurologist says that based on her brain scans, symptoms, test results, and the disease progression, she thinks it is Alzheimer's rather than vascular disease, but I guess it could be a combination of both.

My mother wasn't diagnosed until the age of 73, but we're pretty sure she had it since the age of about 65 and she hid it. She lived alone, and was able to hide it until it was very noticeable. My brother and I thought she was just getting older, and of course in hindsight, we should have known something was up.

Thanks again and I wish you continued good health! :)

mike
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Re: Hi! I'm new, and have ApoE questions

Postby mike » Sun Feb 24, 2019 8:51 am

Lynne wrote:Thanks for the tips! That magnifying glass search feature will come in very handy, and I love the extensive Primer and Wiki. And thanks for the info on mitochondrial problems, I didn't know about that, this is all very new to me. I may try the Keto diet, I am vegan, so it would be a little harder, but is still doable. :)

I believe that most folks doing keto on this site are doing a mostly vegetarian diet. Because of my diabetes, I'm not. But look up diet and keto in the primer and wiki, and the forums, you will find lots to start digging in to and start learning.
Sonoma Mike
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ann9787
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Re: Hi! I'm new, and have ApoE questions

Postby ann9787 » Sun Feb 24, 2019 9:55 pm

Hi,

How can you find out if you have the ApoE gene on Promethease? I just ran my raw data from 23andme and nothing came up. I also ran it through codegen.eu and it said I have a 3.8x risk based on the rs669 gene. I'm just in the beginning of all of this and my head is sort of spinning right now.

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Re: Hi! I'm new, and have ApoE questions

Postby floramaria » Sun Feb 24, 2019 10:26 pm

ann9787 wrote:Hi,

How can you find out if you have the ApoE gene on Promethease? I just ran my raw data from 23andme and nothing came up. I also ran it through codegen.eu and it said I have a 3.8x risk based on the rs669 gene. I'm just in the beginning of all of this and my head is sort of spinning right now.


Hi ann9787,

I just pulled up my Promethease Report to look at it. On mine, the very first category on the report has my ApoE status. At the header of the box is gs141, indicating that I have one ApoE4 allele and one ApoE3. In Promethease, at least at the time I ran my 23 & Me data, gs216 is the designation for someone who carries 2 ApoE4 alleles. My guess would be that if Promethease has not put your ApoE status up near the top of your report, it is probably because you do not carry any copies of the ApoE4 variant. You might try typing ApoE into the search box and see if that yields results.
You, like everyone else, definitely have inherited 2 ApoE genes. The variants are ApoE4, ApoE3, and ApoE2 and you get one from each parent. ApoE4 is correlated with higher risk of developing Alzheimers. You might have 2 copies, one copy or none. But you will definitely have two variants of the ApoE gene. Possible combinations are ApoE4/4, ApoE3/4, ApoE2/4, ApoE3/3 ApoE3/2 or ApoE2/2.
I suggest you have a look at the Primer to gain an understanding of what the ApoE gene is all about. The Primer gives an excellent overview and is a great place to begin.
Functional Medicine Certified Health Coach
IFM/ Bredesen Training in Reversing Cognitive Decline (March 2017)

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Re: Hi! I'm new, and have ApoE questions

Postby ann9787 » Mon Feb 25, 2019 7:09 am

Thank you for replying to my question. I was finally able to figure it out after a lot more reading and it turns out that I am e3/e3 which is neutral but I have the rs669 (g,g) which is not so good. Thanks again,

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Re: Hi! I'm new, and have ApoE questions

Postby NF52 » Mon Feb 25, 2019 9:03 am

ann9787 wrote:Thank you for replying to my question. I was finally able to figure it out after a lot more reading and it turns out that I am e3/e3 which is neutral but I have the rs669 (g,g) which is not so good. Thanks again,
Welcome, ann9787!

Persistence is a wonderful trait, since it means you have an optimistic belief in your own ability to find solutions to thorny problems! So you have several pieces of good news: being ApoE 3/3 is what 75% of people with European ancestry have as their genetic profile, and it brings only about a 10-15% risk of either Mild Cognitive Impairment or dementia by age 85. (Advanced age is of course a risk factor associated with development of MCI or Alzheimer's, but current estimates are that up to a third of cases can be prevented through attention to high risk factors such as smoking, heavy alchohol use, diabetes, obesity, sedentary lifestyles with little exercise, exposure to air pollution and other toxic substances, and high blood pressure.

REVISED: Ann, here is a corrected link to snpedia's entry on rs669: https://www.snpedia.com/index.php/Rs669 with many thanks to "Matisse" for catching my error in entering the number in the earlier reply. It looks like the evidence is not unequivocal that this one SNP raises your risk. Here's a quote from a 2014 study that snpedia shows in their source material: [Emphasis added]
Accumulating studies have evaluated the association of Alpha-2-Macroglobulin gene (A2M) 5 bp insertion/deletion (5 bp I/D, rs3832852) and [b]Ile1000Val (rs669) polymorphisms with Alzheimer's disease (AD) risk, but the results remain inconclusive...We performed meta-analysis of [/b]39 studies involving 8,267 cases and 7,932 controls for the 5 bp I/D polymorphism and 27 studies involving 6,585 cases and 6,637 controls for the Ile/Val polymorphism. Overall results did not show significant association between these two polymorphisms and AD risk in dominant, recessive, and multiplicative genetic models. On the stratification analyses by ethnicity and APOE ε4 status with genotypes of polymorphism sites, similar negative associations were found. The meta-analysis suggests that there is no enough evidence for associations of A2M gene polymorphisms (5 bp I/D, Ile1000Val) with AD risk at present, even after stratification by ethnicity and APOE ε4 with genotypes of polymorphism sites. However, due to the heterogeneity in the meta-analysis, the results should be interpreted with caution.

https://www.ncbi.nlm.nih.gov/pubmed/24756728?dopt=Abstract

I don't expect that you'll need to explore our site much, but if you do, the PRIMER is a great place to start.

Enjoy life in Europe, wherever you are located!
Last edited by NF52 on Mon Feb 25, 2019 5:16 pm, edited 2 times in total.
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Re: Hi! I'm new, and have ApoE questions

Postby Fiver » Mon Feb 25, 2019 10:41 am

Hi Lynne. No worries. There may be studies out there showing negative impacts of SSRIs. I just haven't seen them. I've read a few showing slight benefits, e.g. reduction in risks. Nothing dramatic but no obvious downside in terms of AD. SSRIs can be anti-inflammatory; maybe this explains some of the benefit, I don't know.

Developing some dementia at age 90 is fairly common, perhaps even normal. Personally, I never expected to live anywhere near that long. I don't have those kinds of lucky genes. But dementia in the 65-75 range is something I hope we can avoid.
Four relatives with AD. Concerned, but hopeful. Introverted, but will talk about science.

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Re: Hi! I'm new, and have ApoE questions

Postby Matisse » Mon Feb 25, 2019 12:12 pm

NF52 , Just an FYI, I noticed when reading your reply, Snpedia link is for RS 699. Should be RS 669.

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Re: Hi! I'm new, and have ApoE questions

Postby NF52 » Mon Feb 25, 2019 5:16 pm

Matisse wrote:NF52 , Just an FYI, I noticed when reading your reply, Snpedia link is for RS 699. Should be RS 669.

Deep thanks, Matisse, for catching that! I should have looked more closely when the results showed only an association with hypertension. I have corrected my earlier welcome to ann9787 and am copying her on so that she can also see the corrected entry!
You can be my editor any time!

ann9787 wrote: I was finally able to figure it out after a lot more reading and it turns out that I am e3/e3 which is neutral but I have the rs669 (g,g) which is not so good.

REVISED: Ann, here is a corrected link to snpedia's entry on rs669: https://www.snpedia.com/index.php/Rs669 with many thanks to "Matisse" for catching my error in entering the number in the earlier reply. It looks like the evidence is not unequivocal that this one SNP raises your risk. Here's a quote from a 2014 study that snpedia shows in their source material: [Emphasis added]
Accumulating studies have evaluated the association of Alpha-2-Macroglobulin gene (A2M) 5 bp insertion/deletion (5 bp I/D, rs3832852) and Ile1000Val (rs669) polymorphisms with Alzheimer's disease (AD) risk, but the results remain inconclusive...We performed meta-analysis of 39 studies involving 8,267 cases and 7,932 controls for the 5 bp I/D polymorphism and 27 studies involving 6,585 cases and 6,637 controls for the Ile/Val polymorphism. Overall results did not show significant association between these two polymorphisms and AD risk in dominant, recessive, and multiplicative genetic models. On the stratification analyses by ethnicity and APOE ε4 status with genotypes of polymorphism sites, similar negative associations were found. [b]The meta-analysis suggests that there is no enough evidence for associations of A2M gene polymorphisms (5 bp I/D, Ile1000Val) with AD risk at present, even after stratification by ethnicity and APOE ε4 with genotypes of polymorphism sites. However, due to the heterogeneity in the meta-analysis, the results should be interpreted with caution.

https://www.ncbi.nlm.nih.gov/pubmed/24756728?dopt=Abstract
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