37, just discovered I'm ApoE3/4

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Re: 37, just discovered I'm ApoE3/4

Post by Tincup »

HopefullyOptimistic wrote: Tue Dec 06, 2022 1:33 pm Rather than create a new thread @TinCup. Are there any members of this forums that have mutations on PSEN1, PSEN2, or APP? Or any geneticists that may be able to help me interpret some of my other results.
Not something I've focussed on. However a search separately on each of these terms will likely bring up a number of hits. The search page is here. Search on a computer is the magnifying glass in the upper right of the screen. On a phone it is the magnifying glass icon on the left middle side at the top of the screen.

I'm not aware of geneticists here. There are some lay people who are interested for their own situations.

Separately, @TinCup doesn't do anything on this system to notify me. I happened to see it. The sure way to do it is to quote a post of mine, then delete all the text, except for one space. That way, I'll get an email about the post.
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Re: 37, just discovered I'm ApoE3/4

Post by NF52 »

HopefullyOptimistic wrote: Thu Dec 01, 2022 9:17 am Hi all,

...I've done a ton of research myself these past few days after discovering my 3/4 genotype. I'm writing just for catharsis and support. From what I've read thus far this place is nothing but supportive and has done wonders to assuage my existential dread.

I recently had genetic testing done for reproduction and overall health and I requested to see what sort of predisposition I had to AD. Maybe that was a bad idea because I am now completely consumed with the news and re-considering if I even want to have children....

... My dad's parents however both lived into their 80s....
On my mom's side there is no history of AD. My maternal grandparents lived until 87 and 89.
...
My approach ...
I don't really have a question per se, just would love some support and some words of wisdom from the older Apoe4s here who have lived full and happy lives and are still managing their cognition into their 70s....
A belated welcome, HopefullyOptimistic!

I one of those people you wanted to hear from, with two copies of ApoE4, 70 years old, who is looking forward to adding many more years of marriage to my inexhaustibly patient husband of 42 years (who rarely gets to tell a complete story without me excitedly offering some comment), our three wonderful ApoE 3/4 adult children (close in age to you) and our two grandchildren. And I have not been a perfect lifestyle practitioner for 70 years! What I do have, and you have also, is a family history of some people who made it into their 80's and 90's with normal cognition, a personal history of never being a big drinker, and rarely drinking now, keeping my glucose in a good range as measured by an HbA1c test, insulin resistance good (another OTC blood test) inflammation low (C-reactive protein test). We all have factors in our genes and in our environments that can dial down our risk. Finding where yours might be higher or lower with some of the blood tests/biomarkers recommended by Dr. Stavia in her Primer Appendix:Biomarkers and maybe using some Direct to Consumer Lab Testing Options will give you peace of mind, I'm predicting. It can also be the start of a yearly "check-up" on areas you want to monitor.

The risk of ApoE 3/4 for a diagnosis of EITHER mild cognitive impairment (MCI) or dementia by the age of 85 (the average life span for someone my age in the US today) is estimated at 20-25%; your risk, as someone who has decades of healthy habits to build on, is almost certainly well under that. I quoted above from the healthy family history you have; because looking only at those in your family who struggled with alcoholism is no more relevant to you than looking at the history of your ancestors who might have had farm injuries, or lived in smog-ridden cities.

You are not them! Enjoy having a life filled with purpose, joy and hope--from someone whose "signature" says we're both hopeful people!

Nancy
4/4 and still an optimist!
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Re: 37, just discovered I'm ApoE3/4

Post by NF52 »

HopefullyOptimistic wrote: Tue Dec 06, 2022 1:33 pm Rather than create a new thread @TinCup. Are there any members of this forums that have mutations on PSEN1, PSEN2, or APP? Or any geneticists that may be able to help me interpret some of my other results.

23andMe is showing a ton of PSEN1 variants. But all homogenous alleles that are listed as "common in clinvar" and not pathogenic. But I am still scared beyond words.
Hi Hopefully,

You can put that worry about PSEN1 variants to rest!

When you have two of the same "varant" in PSEN1 genes, it means you are "homozygous" for that variant.

Unlike having two copies of ApoE 4, it's GOOD thing to have those C/C, G/G or T/T variants in PSEN1. A "variant" is not a "mutant"; it really is just one of several possible "variations" in gene expression. When you see "common in clinvar"; that means you have the common version--the one that does NOT carry a risk for Early Onset Alzheimer's disease.

23&me is showing you a whole "ton of variants" because PSEN1 is a busy gene, with lots of smaller parts:
The PSEN1 gene provides instructions for making a protein called presenilin 1...Presenilin 1 carries out the major function of the complex, which is to cut apart (cleave) other proteins into smaller pieces called peptides...

This cleavage is an important step in several chemical signaling pathways that transmit signals from outside the cell into the nucleus. One of these pathways...is essential for the normal growth and maturation ... of hair follicle cells and other types of skin cells [and] is also involved in normal immune system function.
https://medlineplus.gov/genetics/gene/psen1/

Like you, I have the "common" homozygous variants of the PSEN1 gene on 23&me and am happily still getting hair follicles and immune system functioning at age 70. So no worries for you!

Nancy
4/4 and still an optimist!
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Re: 37, just discovered I'm ApoE3/4

Post by HopefullyOptimistic »

Nancy! I started crying when I read your post. Thank you for replying. Truly.

Discovering my ApoE4 gene I could stomach. I was looking forward to a long life well lived but the flood of PSEN1 "variants" that appeared on 23andMe put me under a dark cloud that I have not been able to shake. What an irresponsible company. I was about to yank my entire 401k!

I had been trying to find a genetic counselor to confirm what I thought -- that homogenous and common in clinvar means that I'll be fine and not at risk of losing my cognition in my mid 40s like all the articles I had read.

I am grateful for you and this community.

Thank you again for lifting this cloud.
NF52 wrote: Wed Dec 07, 2022 5:05 pm
HopefullyOptimistic wrote: Tue Dec 06, 2022 1:33 pm Rather than create a new thread @TinCup. Are there any members of this forums that have mutations on PSEN1, PSEN2, or APP? Or any geneticists that may be able to help me interpret some of my other results.

23andMe is showing a ton of PSEN1 variants. But all homogenous alleles that are listed as "common in clinvar" and not pathogenic. But I am still scared beyond words.
Hi Hopefully,

You can put that worry about PSEN1 variants to rest!

When you have two of the same "varant" in PSEN1 genes, it means you are "homozygous" for that variant.

Unlike having two copies of ApoE 4, it's GOOD thing to have those C/C, G/G or T/T variants in PSEN1. A "variant" is not a "mutant"; it really is just one of several possible "variations" in gene expression. When you see "common in clinvar"; that means you have the common version--the one that does NOT carry a risk for Early Onset Alzheimer's disease.

23&me is showing you a whole "ton of variants" because PSEN1 is a busy gene, with lots of smaller parts:
The PSEN1 gene provides instructions for making a protein called presenilin 1...Presenilin 1 carries out the major function of the complex, which is to cut apart (cleave) other proteins into smaller pieces called peptides...

This cleavage is an important step in several chemical signaling pathways that transmit signals from outside the cell into the nucleus. One of these pathways...is essential for the normal growth and maturation ... of hair follicle cells and other types of skin cells [and] is also involved in normal immune system function.
https://medlineplus.gov/genetics/gene/psen1/

Like you, I have the "common" homozygous variants of the PSEN1 gene on 23&me and am happily still getting hair follicles and immune system functioning at age 70. So no worries for you!

Nancy
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Re: 37, just discovered I'm ApoE3/4

Post by NF52 »

HopefullyOptimistic wrote: Wed Dec 07, 2022 5:40 pmThank you again for lifting this cloud.
Glad to help!

Enjoy that 401K in another 30 years or sooner; every day you are writing your own life story of resilience--plan to share it with your grandchildren!

Enjoy the holidays!
Nancy
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Re: 37, just discovered I'm ApoE3/4

Post by TCHC »

Hi HopefullyOptimistic
I just wanted to say, well done for doing your research, taking the healthy approach to life, working on prevention before it ever becomes an issue and doing it all despite the jarring change noticed by your peers. It's heartening to hear your story.
I'm not "an older ApoE4" but my Mum is on the protocol and doing so much better now and I, like you, am on prevention.
I'm in the UK and this isn't well known over here, my newfound purpose in life is to tell more people in the UK and give some hope!
Lindsey
TCHC - Lindsey Byrne - The Cognitive Health Coach - UK
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