BIN1 + APOE44 ?

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j.stevenson01
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BIN1 + APOE44 ?

Post by j.stevenson01 »

Is anyone else on here homozygous for the top 2 Alzheimer's genes as ranked by Alzgene, those being:

APOE 44
BIN1 rs744373, minor allele G is the risk allele. OR = 1.35 for homozygotes.


I am always worrying about getting early-onset Alzheimers, thinking about how these genes may interact to cause beta-amyloid to accumulate much earlier. BIN1 has been shown to affect BACE1 trafficking and beta-amyloid production.

Perhaps it is ridiculous to worry about BIN1 given its low odds ratio in comparison to APOE? and its high frequency (50% of people have at least one minor allele). Discovering my APOE44 status has ruined my life, and finding out that I have BIN1 GG is just another kick in the teeth.

This knowledge has made me suicidal, and the fact that Alzheimer's is 80% genetic and the rest just comes down to essentially being healthy makes me feel there was no point in finding out. I don't share the same faith many of you do in Dale Bredesen, as much as I want to believe I don't see enough evidence to support his claims.
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NF52
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Re: BIN1 + APOE44 ?

Post by NF52 »

j.stevenson01 wrote:Is anyone else on here homozygous for the top 2 Alzheimer's genes as ranked by Alzgene, those being:

APOE 44
BIN1 rs744373, minor allele G is the risk allele. OR = 1.35 for homozygotes.


I am always worrying about getting early-onset Alzheimers, thinking about how these genes may interact to cause beta-amyloid to accumulate much earlier. BIN1 has been shown to affect BACE1 trafficking and beta-amyloid production.

Perhaps it is ridiculous to worry about BIN1 given its low odds ratio in comparison to APOE? and its high frequency (50% of people have at least one minor allele). Discovering my APOE44 status has ruined my life, and finding out that I have BIN1 GG is just another kick in the teeth.

This knowledge has made me suicidal, and the fact that Alzheimer's is 80% genetic and the rest just comes down to essentially being healthy makes me feel there was no point in finding out. I don't share the same faith many of you do in Dale Bredesen, as much as I want to believe I don't see enough evidence to support his claims.
Welcome, my 4/4 "relative"--since I come from folks in Scotland, England, Germany, Austria and Italy, I figure I'm related to most people with that ancestry with ApoE4.

Please, if you are truly feeling suicidal right now, call a hotline and talk to someone--anyone.

And maybe trust me for just a bit--someone who is 69, has those same 4/4 genes (though not B1N1) along with sky-high Lp(a) and a family history of AD and heart disease---and yet is still scoring normally on cognitive tests (which I took every 3 months in a clinical study from 2017-2020 and take online now. We are more than these genes!

ApoE4 is NOT one of the dominant Early-Onset Alzheimer's gene. I've been on panels with researchers since 2018 and get to have sidebar conversations with them. They all say that doing things to keep your brain active (cognitive reserve) and healthy (cognitive resilience against pathology) absolutely will reduce risk--by a factor of 1/3 in many cases.

It is a cruel rollercoaster of emotions that happens to us when we find this out--a real punch to the gut. And yet--it is also a reason to say "not yet, you don't get me--and maybe never!" Why would I pass up more time with my husband, my adult children, my grandchildren, the chance to learn more about how to keep myself healthy--or how to avoid getting poison ivy every time I attack my garden.

You've reached out to us--let us become the community of support for you. Spend some time reading about people on here in their 70's and 80's with ApoE 4/4. Tell us some more about yourself--your age, your values and what you'd love to do this year. And then let us show you how it's possible.

Alzheimer's is a "multi-factorial" disease, with many upstream causes and multiple presentations. It's no more determined that my dad and his identical twin brother--who dressed, looked and joked the same, but died 7 years apart from completely different causes--neither of the Alzheimer's.

Thank you for sharing your pain--let us take some of it from you.
4/4 and still an optimist!
j.stevenson01
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Re: BIN1 + APOE44 ?

Post by j.stevenson01 »

NF52 wrote:
j.stevenson01 wrote:Is anyone else on here homozygous for the top 2 Alzheimer's genes as ranked by Alzgene, those being:

APOE 44
BIN1 rs744373, minor allele G is the risk allele. OR = 1.35 for homozygotes.


I am always worrying about getting early-onset Alzheimers, thinking about how these genes may interact to cause beta-amyloid to accumulate much earlier. BIN1 has been shown to affect BACE1 trafficking and beta-amyloid production.

Perhaps it is ridiculous to worry about BIN1 given its low odds ratio in comparison to APOE? and its high frequency (50% of people have at least one minor allele). Discovering my APOE44 status has ruined my life, and finding out that I have BIN1 GG is just another kick in the teeth.

This knowledge has made me suicidal, and the fact that Alzheimer's is 80% genetic and the rest just comes down to essentially being healthy makes me feel there was no point in finding out. I don't share the same faith many of you do in Dale Bredesen, as much as I want to believe I don't see enough evidence to support his claims.
Welcome, my 4/4 "relative"--since I come from folks in Scotland, England, Germany, Austria and Italy, I figure I'm related to most people with that ancestry with ApoE4.

Please, if you are truly feeling suicidal right now, call a hotline and talk to someone--anyone.

And maybe trust me for just a bit--someone who is 69, has those same 4/4 genes (though not B1N1) along with sky-high Lp(a) and a family history of AD and heart disease---and yet is still scoring normally on cognitive tests (which I took every 3 months in a clinical study from 2017-2020 and take online now. We are more than these genes!

ApoE4 is NOT one of the dominant Early-Onset Alzheimer's gene. I've been on panels with researchers since 2018 and get to have sidebar conversations with them. They all say that doing things to keep your brain active (cognitive reserve) and healthy (cognitive resilience against pathology) absolutely will reduce risk--by a factor of 1/3 in many cases.

It is a cruel rollercoaster of emotions that happens to us when we find this out--a real punch to the gut. And yet--it is also a reason to say "not yet, you don't get me--and maybe never!" Why would I pass up more time with my husband, my adult children, my grandchildren, the chance to learn more about how to keep myself healthy--or how to avoid getting poison ivy every time I attack my garden.

You've reached out to us--let us become the community of support for you. Spend some time reading about people on here in their 70's and 80's with ApoE 4/4. Tell us some more about yourself--your age, your values and what you'd love to do this year. And then let us show you how it's possible.

Alzheimer's is a "multi-factorial" disease, with many upstream causes and multiple presentations. It's no more determined that my dad and his identical twin brother--who dressed, looked and joked the same, but died 7 years apart from completely different causes--neither of the Alzheimer's.

Thank you for sharing your pain--let us take some of it from you.
Thank you for your reply, I feel like if it were just APOE 44 I would be fine, knowing the statistics from 23andme they really don't seem bad. It is the combination of the two that worries me so much. Having a 4% chance at 65 and a 25% at 75 and a 50% chance at 85 are honestly what I would have expected in the average person before I found out about all this. I am scared of getting early-onset Alzheimer's.

I am 19, I enjoy aircraft scale models, I have Asperger's.

I receive lots of help on the NHS and privately with CBT psychologists, none of it seems to help. I tell them that I've opened pandora's box and that there is no unseeing what is inside. Everyday is pain, but I keep going for my family.

Regards,
Joseph
APOE 4/4.
NF52
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Re: BIN1 + APOE44 ?

Post by NF52 »

j.stevenson01 wrote: Thank you for your reply, I feel like if it were just APOE 44 I would be fine, knowing the statistics from 23andme they really don't seem bad. It is the combination of the two that worries me so much. Having a 4% chance at 65 and a 25% at 75 and a 50% chance at 85 are honestly what I would have expected in the average person before I found out about all this. I am scared of getting early-onset Alzheimer's.

I am 19, I enjoy aircraft scale models, I have Asperger's.

I receive lots of help on the NHS and privately with CBT psychologists, none of it seems to help. I tell them that I've opened pandora's box and that there is no unseeing what is inside. Everyday is pain, but I keep going for my family.

Regards,
Joseph
. Hi Joseph!

Thank you so much for replying to me--you must be a night owl over there in the UK. I know lots of people--some of them related to me--with Asperger's. In fact, one of my favorite jobs involved helping parents and teams of teachers meet the exciting minds of people with Asperger's where they are--and using sensory rooms, cognitive behavioral therapy and their own strengths and interests to make life with us "neuronal-typicals" a little easier. I bet you have an eye for detail on those aircraft scale models that would be the envy of the RAF! As for me, I can't draw as well as the average 6 year old--just goes to show we are more than our ApoE 4/4 status.

Here's the thing about those statistics: They apply to people OLDER THAN ME! The best meta-analysis I've seen was done on four large population studies ( two in the US, one in Rotterdam) and data from US centers that tested people with memory issues in the late 1990's and early 2000's. They found that people with ApoE 4/4 who were already 60 years old back then had a VERY low risk of diagnosis before the age of 65. It rose slowly from 65-70, then higher from 70-75. And then a funny thing happened: The people who had ApoE 4/4 and were older than 75 continued for the most part of be healthy. The obvious conclusion: There are "risk" and "resilience" factors. People whose brains do complex problem-solving from a young age (i.e. YOU) build up tons of extra neurons and have multiple pathways to use for any given problem. Those are the one who appear to have "brain resilience". People with good cardiovascular health (which can be helped at any age) keep their brains resistant to inflammation and also stay healthy.

In the same way that we don't use the same phones we used when I was 19, you won't use the same strategies or medicine to stay healthy that I use. Scientists have JUST found which kinds of tau tangles are the bad actors in our brains--decades after amyloid shows up. So guess what: They'll find ways to shut that off, way before you need to worry about it.

Please share with your therapists and your family how you're feeling. Maybe they will have some suggestions for some short-term supports. In the meantime, we're always here for you, Joseph.

NF52
4/4 and still an optimist!
Sara Barthel
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Re: BIN1 + APOE44 ?

Post by Sara Barthel »

j.stevenson01 wrote:I am always worrying about getting early-onset Alzheimers, thinking about how these genes may interact to cause beta-amyloid to accumulate much earlier. BIN1 has been shown to affect BACE1 trafficking and beta-amyloid production.

Perhaps it is ridiculous to worry about BIN1 given its low odds ratio in comparison to APOE? and its high frequency (50% of people have at least one minor allele). Discovering my APOE44 status has ruined my life, and finding out that I have BIN1 GG is just another kick in the teeth.
Hi j.stevenson01,
I wanted to welcome you to apoe4.info, and just acknowledge that discovering our ApoE status can be very distressing for many of us. I hope that you will seek support from a practitioner you do trust who can help you navigate this. I also hope that you find hope and support through this forum. I am a support team intern and wanted to share a few useful links with you to help familiarize you with this site.

My favorite resource is the Primer, written by one of our member physicians, Stavia, who is APOE4/4. It is great introduction to ApoE4, biochemistry, and possible prevention strategies in addition to exploring areas such as the science behind the ApoE4 gene and the lifestyle factors that impact its expression. It is a wealth of information - a great place to start and to come back to time and again.

Our wiki Index offers a wealth of additional information and details the muti-factorial approach to taking control of your brain health. Useful for searching specific topics of interest.

Enjoy your learning experience in the forum and we are glad you are here.

Sara Barthel
j.stevenson01
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Re: BIN1 + APOE44 ?

Post by j.stevenson01 »

Thank you both for your replies.

I am feeling a little bit better today, I have an appointment with my psychiatrist so hopefully that goes well.

Regards
Joseph
APOE 4/4.
circular
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Re: BIN1 + APOE44 ?

Post by circular »

Welcome Joseph, I just wanted to say that for me, and I think many others here, at first and for a while after finding out our e4 status, awareness of it stayed all too painfully and fearfully fresh every day for a while, but with time it takes more of a back seat.

I don’t recall my BIN1 result offhand, but I’m homozygous for another AD risk gene, CR1, about which there is no advice available. My parent who had Alzheimer’s herself and in her family did not have ApoE4 but was also homozygous on CR1. I find this disconcerting similar to how you feel piling BIN1 and E4 upon each other is disconcerting (to say the least). After all, there’s a strong family history and she wasn’t E4. Meanwhile, I got my one E4 from my brainy father. I suspect that most people with E4 have other AD risk genes, but we all also probably have some protective genes. AD genetics is extremely complicated, and I think, while understanding the fear, that it’s reasonable to embrace ‘I don’t know what will happen but I will do the best I can to support my health’ in place of trying to predict.

There have been some good lifestyle studies that aren’t as complicated as Dr. Bredesen’s showing that E4 individuals get cognitive benefit through lifestyle. Check out the MIND, FINGER and PREDIMED studies. Exercise is strongly tied to benefitting E4s. So keep learning and you may find sufficient reason for hope outside of the complicated and expensive Bredesen Protocol. I often rely on these sorts of lifestyle clinical trials as pointing to some of the largest risk modifiers we have, even though I like Dr Bredesen’s approach overall and dabble in it on my own when I can.

I’m glad you have such a stable support team. It suddenly dawned on me that if they can hook you up with a genetic counselor you may find that very helpful.

Circ
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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Re: BIN1 + APOE44 ?

Post by circular »

j.stevenson01 wrote:Is anyone else on here homozygous for the top 2 Alzheimer's genes as ranked by Alzgene, those being:

APOE 44
BIN1 rs744373, minor allele G is the risk allele. OR = 1.35 for homozygotes.
Shoot, I just lost a whole post. In short, it noted that the Alzgene ranking of AD genes by risk is from 2011 and very outdated. I don't know what status BIN1 would have now, and no doubt it's important, but I would hold off on thinking of it as the second riskiest AD gene without further corroboration based on current science.

Also, if you used Promethease to retrieve your SNP results, be aware that I have found it to be highly unreliable for this purpose, and at least one other person found it unreliable as well. If you can search your raw data at 23andMe, if you tested there, that would be best.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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