Found out I carry the PSEN1 gene is this a death sentence?

[Starfish77]

Giftsplash, I certainly care about you and am with you in spirit. I can't add anything to the information others have shared. I hope you will to be in touch with us as you learn more with your research.

[MarcR]

I'm sorry to hear this upsetting news, Giftsplash. Your surprise and current inability to identify relatives cut down in their 40s and 50s by early onset AD are powerful counterweights - it seems likely that you lack the full EOAD genotype.

J11, I love your post on using Ancestry.com - very helpful.

[J11]

Thank you MarcR for the encouragement!

Your remark has motivated me to get on the stump and push this one to the people!
There is a woeful lack of insight in the community of how much horsepower exists on sites
such as GEDmatch and Ancestry.com to push AD genetics to victory. If government or others
do not have the wits or compassion to make this happen, then We the People will need to push
it over the line.

What is it that is not clear enough here?
1-2 million Americans are epsilon 4 carriers and yet have the protective RAB10 variant.
This probably means that they are actually low risk for dementia.
Yet, 18 months after ICAD 2016 the protectiveness of the RAB10 variant is still highly uncertain.

Basically 60 million Americans APOE4 carriers and 100s of millions of APOE4 carriers elsewhere in the
world are asking themselves right now will I or will I not need to plan for severe neurodegenerative illness?

'Bout time we start flexing epsilon 4 socio-political muscle to find out!
The answer to this question worth over $100 billion to 1 million Americans involved to have answered;
it deserves at least a $10,000 effort to find out what is going on here. This should be what the
political process is all about: coordinate organized responses to solve the problems
that exist beyond the level of individual control. If they don't want to pick this one up
then there are now a range of online tools, to make it happen in other ways.

[giftsplash]

It's been a tough week. I am still waiting for a genome counselor to do full analytics. I did verify that neither of my parents carry the PSEN1 mutation. However I am not sure if that offers any solace.
Maybe someone can shine some light on this
http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002270

[giftsplash]

Wanted to give everyone an update on my status. I found out through Prometheus that I carry the PSEN-1 mutation. After speaking to a genome counselor I found out that this guarantees that I will have early onset of dementia.

My first glimmer of hope came when I ran my girlfriends DNA through Prometheus and found out that she carries the exact same mutation. The odds of PSEN-1 De Novo is about 1 in 75,000. The odds of 2 people in the household with the same mutation is roughly 1 in 5.6 billion.

After getting tested for this mutation with a company that specializes in PSEN-1 I found out that this is a false positive and that I am perfectly healthy. However it’s been a very rough last few months as you can imagine.

Few take aways:

1) Do not trust 23 and Me data to tell you the whole story. I wonder how many people on these boards might not even be APOE4’s 
2) I am not so certain that PSEN-1 has to always lead to early onset of dementia since all the studies I looked at tested people with dementia for PSEN-1, people without it were never tested. So there might be some bias in the studies.

[Maryann]

After getting tested for this mutation with a company that specializes in PSEN-1 I found out that this is a false positive and that I am perfectly healthy. However it’s been a very rough last few months as you can imagine.

Few take aways:

1) Do not trust 23 and Me data to tell you the whole story. I wonder how many people on these boards might not even be APOE4’s 
2) I am not so certain that PSEN-1 has to always lead to early onset of dementia since all the studies I looked at tested people with dementia for PSEN-1, people without it were never tested. So there might be some bias in the studies.

Oh my goodness giftsplash! You are perfectly healthy! I am So happy to hear this! I'm sorry that happened to you, and hope this experience can somehow bring something positive in it's wake.

[Julie G]

Thank you for sharing your good news. Happy dance for you, my friend!

I wonder how many people on these boards might not even be APOE4’s

FWIW, I'm a TrueHealthLab confirmed 4/4. No get-out-of-jail-free card for me... yet

[Searcher]

Happy for you, giftsplash!

This community does so many good things for so many people.

One of them could perhaps be educating people about the reliability/unreliability of direct-to-consumer genetic tests.

Another could be educating doctors about the need for fully informed consent and quality control of labs before sending samples for genetic testing.

A third could be a list of highly informed genetic counselors, who can provide comprehensive and reliable whole-genome association information. Currently some people probably over-estimate their risks while others greatly under-estimate them. The quality of counseling can make a big difference.

[CoachDD]

Wow, Giftsplash. . . what an emotional ride you've been on! I'm so sorry about that and so VERY glad it ended the way it did!! Did your ApoE4 result change as well?

I've been on the same painful journey to find out if I am at risk for early onset as well. I am 50 years young with confirmed e3/e4 (based on 23andMe and confirmed through Boston Heart labs). I have two other markers: one for PSEN1 (it's the SNP recognized as protective - unfortunately, I do NOT have it) and one for APP.

There are other gene markers that are under investigation for AD - the common ones I found on many sites are: APP, PSEN1, PSEN2, MAPT, CLU, CR1, PICALM and TREM2. There are many others that are currently being reviewed.

I am currently working with a Bredesen trained doc - I was officially diagnosed with MCI (mild cognitive impairment) last week, so a PET Scan and an MRI with Neuro Quant are now scheduled. Prayers welcomed!!

I understand why many ask about familial AD - yet, our family did not see it. That's because, quite unfortunately, most of my ancestors died young (mostly from heart disease). . . so my gut tells me they all died BEFORE AD reared its ugly head. My parents died quite young - my mother was sickly most of her adult life (obese since I was born - she also had uncontrolled diabetes and died at age 66 after multiple (mini) heart attacks which lead to congestive heart failure). My father had a quad-bypass in his mid 60s and then a stroke - he died in his sleep at age 72. My maternal grandmother died of a massive heart attack at 39 and the remaining grandparents died in their 60s/70s (all heart issues!!). All of my aunts and uncles have died (6 of them - many had diabetes, two died from massive heart attacks in their 50s, three died of heart issues in their 60s and only one died from liver cancer in her early 70s (although she had heart issues!)). As far as I know, only one had an autopsy. I should add: I am the baby of 16 cousins - 5 have died already (2 from cancer, although they had heart issues) and only one has made it past the ripe old age of 60 (yet she is in a rehab center - had a stroke in her mid-50s and recently had heart surgery!). YIKES - scary stuff!!!!!!

I appreciate the information J11 posted earlier about Ancestry.com and the other GEDMatch site - I am definitely looking into that.

I'm sharing all of this to enlighten others who read this post and are concerned about early onset - just because AD is not in your family history, that does NOT mean you are not at risk (especially if you carry one or two ApoE4 allele along with the other gene markers).

I welcome any and all feedback on this subject!

[circular]

I also discovered that the E4 in me (3,4) came from the side of the family with heart issues and not the side with four cases of Alzheimer's.

Coach, with that many early deaths by heart problems, I can't help but ask if your family has a tendency to having hypermobile joints ('double joined' or bendy or hyperextensive). I don't want to send you barking up any wrong trees, but this sort of pattern, if due to vessel ruptures, can also occur in a family with a inherited connective tissue disorder.