New (double E4) and research question about family history

[Saskia]

Hello all

What a great, informative and respectful forum this is. I signed up after reading these boards for a couple of months and am currently reading the Bredesen book.

When I found out that I carry double apoE4 after a test that I mostly did to learn about my heritage I was surprised as I have no family history of Alzheimer's disease whatsoever (in my rather large family). My dad is 87 and starting to have very mild cognitive decline but nothing noteworthy. My mother is younger and fine. Not one of my grandparents or older aunts and uncles have been diagnosed with AD or shown signs beyond mild "what was I in the kitchen for again" type confusion after age 85.

Has anyone seen this bit of research (https://www.jneurosci.org/content/26/22/6069) where lack of family history of AD seems to imply a better prognosis (or at least lack of early clinically measurable cognitive decline) for apoE4 carriers? Has anyone seen other research in that area, either to confirm or disprove these findings or to attempt to find out the underlying reason?

I did look across this forum to prevent asking an already answered question so apologies if it has been discussed elsewhere.

Many thanks

[slacker]

When I found out that I carry double apoE4 after a test that I mostly did to learn about my heritage I was surprised as I have no family history of Alzheimer's disease whatsoever (in my rather large family). My dad is 87 and starting to have very mild cognitive decline but nothing noteworthy. My mother is younger and fine. Not one of my grandparents or older aunts and uncles have been diagnosed with AD or shown signs beyond mild "what was I in the kitchen for again" type confusion after age 85.

Has anyone seen this bit of research (https://www.jneurosci.org/content/26/22/6069) where lack of family history of AD seems to imply a better prognosis (or at least lack of early clinically measurable cognitive decline) for apoE4 carriers? Has anyone seen other research in that area, either to confirm or disprove these findings or to attempt to find out the underlying reason?

Welcome Saskia! Thanks for looking elsewhere on the site before posting your excellent question; even if the topic has been discussed, it can be difficult to find. So please be comfortable asking.

I think other members have discussed the possibility of genes that can protect against AD, and this seems likely in the situation you find in your family. Here is one for example. Hopefully someone else will chime in. Lifestyle most likely has an impact as well.

[Flo]

What a great, informative and respectful forum this is.

Dear Saskia,

Welcome to the forum and we're so pleased that you find this environment safe enough to be able to post your question - you've got us all intrigued now and hopefully someone will be able to shed some light on it.

It sounds like you know your way around the forums quite well already, but here's a link to our "how-to" guide just in case, which might help you navigate through searches for example. There is also some fantastic information in the primer, especially regarding the impact of lifestyle, which you might like to check out if you haven't already done so. I wonder how the information in that section compares to your family's lifestyle?

Glad to have you here, and if you have any more questions, please don't hesitate to ask!

All the best
Flo

[Saskia]

The lifestyle story is indeed interesting. To paint a rough picture - we're in the Netherlands where base levels of activity may be slightly higher than in parts of the US thanks to cycling as a common means of transport. My dad always did physical work as well as lots of running and daily exercise. My mum is moderately active. Thankfully nobody in the extended family is overweight. So much for the good behaviours. My dad smoked from his 14th until he was 75 and so did many of his brothers. Crazy - and unfair how they seem so unaffected by such a terrible habit. And in no way is our national diet low-carb. Processed foods are probably a bit less prevalent but I wouldn't bet a statistically significant difference on it! Long story short: my family's lifestyle component is at best ambiguous. I do plan to go low carb and as I'm not sure either of my parents is E4/E4 i.e. I may be the most predisposed one so far.

[Saskia]

I think other members have discussed the possibility of genes that can protect against AD, and this seems likely in the situation you find in your family. Here is one for example. Hopefully someone else will chime in.

Thank you! It would be great if any of the commercially available gene testing services could test for the Rs142787485 variant on RAB10, which seems to be the main protective factor based on that article. 23andme does not seem to do it in any of its versions. Certainly not in V4 which I have.

[Flo]

Long story short: my family's lifestyle component is at best ambiguous. I do plan to go low carb...

That is really fascinating in itself! Which does make one wonder whether other factors are at stake, such as sleep, stress, sense of community and purpose etc.
There are some amazing recipes from our members on the site to help you go carb free, and if you have any of your own, please feel free to share them!

Flo

[SusanJ]

Has anyone seen other research in that area, either to confirm or disprove these findings or to attempt to find out the underlying reason?

Hallo Saskia!

I suspect that the family history connection has much to do with other genes that increase or decrease risk. One of the best places to look quickly at your specific genes would be to use Promethease. You can upload your 23andme data, run the analysis, then check on the results specific to Alzheimer's by searching for it in the search box. The genes that are listed might give you a clue to your family genetics.

[Saskia]

I suspect that the family history connection has much to do with other genes that increase or decrease risk. One of the best places to look quickly at your specific genes would be to use Promethease.

Thank you Susan! My Promethease results don't paint much of a consistent picture. A bunch of my other Alzheimer related risk results are green, a bunch are red, and I'm not sure their significance is big enough (or even quantified yet), and some may simply co-occur with e4 and therefore not be an additional factor. Are you aware of a thread in which all the other Alzheimer-related Promethease data from 23andme users is discussed that you know? I've searched but haven't found it yet.

[SusanJ]

Are you aware of a thread in which all the other Alzheimer-related Promethease data from 23andme users is discussed that you know?

Try Alzpedia: https://www.alzforum.org/alzpedia for a current list. Then you can probably use the specific gene to see if it's been discussed here.

[mike]

The lifestyle story is indeed interesting. To paint a rough picture - we're in the Netherlands where base levels of activity may be slightly higher than in parts of the US thanks to cycling as a common means of transport. My dad always did physical work as well as lots of running and daily exercise. My mum is moderately active. Thankfully nobody in the extended family is overweight. So much for the good behaviours. My dad smoked from his 14th until he was 75 and so did many of his brothers. Crazy - and unfair how they seem so unaffected by such a terrible habit. And in no way is our national diet low-carb. Processed foods are probably a bit less prevalent but I wouldn't bet a statistically significant difference on it! Long story short: my family's lifestyle component is at best ambiguous. I do plan to go low carb and as I'm not sure either of my parents is E4/E4 i.e. I may be the most predisposed one so far.

Saskia, you say that processed foods are less - how about added sugars and high fructose corn syrup? While I believe low carb is important, I think sugar and fructose will turn out to be the worse problem. China had very little diabetes eating heavy carb (rice) diet, but it was not until sugar consumption went up that diabetes went up.