The gene that could replace APOE4 as Alzheimer's predictor

[deborahk]

Hello Friends,

I thought this article may be of interest to you all.

This Gene May Oust ApoE4 as Genetic Predictor of Alzheimer’s
https://www.beingpatient.com/tomm40-gene/

Here's some feedback we got from a researcher we asked to comment about the study:

"The late Allen Roses MD had discovered the TOMM40 gene more than 10 years ago. He made the very same claim but did not get much traction with the medical and scientific audiences. The study you posted is confirmatory of what Allen said for years. This finding was the crux of the enrichment strategy for the Takeda TOMMORROW study. I am glad to see his findings independently confirmed."

Another researcher has indicated that there is not yet enough research yet to determine how clinically significant this discovery is.

If you have any questions about it, please go on http://www.beingpatient.com and send us your question in the comments section of this article. Alternatively you can email us directly at info@beingpatient.com. We are getting ready to launch a beta Q&A section where we take questions from our community directly to the 'experts' for answers, which we will publish on our site. We would love your feedback and any questions you have on this or any other topic.

Many thanks!

Deborah

[circular]

This is really interesting new information on TOMM40 in a very large dataset Deborah! Thanks for keeping us in your loop!

I think others here will also benefit by reading the EurekAlert article your article provides a link to. I was intrigued by:

1) the notion that one needs to look at the difference between immediate and delayed recall (another good reason for me to hate the MMSE that people diagnosed with Alzheimer's keep passing), and

2) the suggestion that some effects that have been attributed to APOE4 may actually be sure to the TOMM40 variant.

[Stavia]

too scary to even contemplate looking at mine.

Sent from my SM-G930F using Tapatalk

[circular]

My question is this (can I post it here so others can see I'm submitting it?):

Some of us have noticed in prior posts about TOMM40 that while we have APOE4 we do not have the TOMM40 variant, or are 4/4 and heterozygous (would need to confirm that one), even though they're supposed to be linked. I'm wondering if anyone knows what percentage of 3/4s and 4/4s are exceptions like this. The combos with percentages, if available, should be:

3/4 with variant homozygosity at TOMM40
3/4 with normal homozygosity at TOMM40
3/4 with heterozygosity at TOMM40
4/4 with variant homozygosity at TOMM40
4/4 with normal homozygosity at TOMM40
4/4 with heterozygosity at TOMM40

Not sure if we have any APOE2s on the forum.

[Ksusiedal]

Circular,
Can I ask how you found out whether or not you have the TOMM40 variant? What testing source did you use? Thanks.

[circular]

Hi K,

I'm heading to bed so for now let me link to this recent post by Julie where she includes the two relevant TOMM40 SNPs. (Note that just last month our thinking was that TOMM40 may not be a big player, but this new study appears to suggest otherwise.)

I believe it's the G value on either SNP that's the undesirable variant. If you've tested at 23andM3 you can view your raw data there, or run it through the Promethease program online which will allow you to search for it (about US $5-10). Likewise you can run raw data from other direct to consumer tests through Promethease and search there (eg, Ancestry.com or FTDNA data).

[Julie G]

It might be worth mining previous discussions on TOMM40. I found 59 hits. You can see here.

[Ganesha]

TOMM40 is brand new to me. I'm learning new things already!

I checked my Promethease report and now know that I am a 3/4 that is heterozygous for the relevant TOMM40 SNP's. I am curious if anyone knows what researchers believe/expect the break down looks between the possible ApoE combinations?

Also, I typed TOMM40 in the search bar at Promethease, and the first red box I got was for rs1260326(T,T). It states nothing about AD, but that this SNP increases risk for gout and also has an association with CRP. I found it interesting as my latest hs-CRP is elevated at 7.6. Anybody know anything about this one and/or have the same variant?

Thanks again for the forum!

[maddanwill]

Yep! Promethease confirms I am a 3/4 AND carry the TOMM40 rs2075650 (A;G). Stunned. I thought I would hack the ApoeE4 gene and ride into the sunset....not so fast. AND onset is 7 years earlier?!! That was a big study too. Not easy to poke holes in.

So then I went to Julie's threads re the TOMM40 and saw that the FOXO3 was protective and thought "maybe I have the good FOX gene so I went back to Promethease....nope: FOXO3 rs 2802292 (T, T) and it says....

"Less likely to live to 100. Unfortunately, this version of FOXO3 has reduced longevity. It has lower insulin sensitivity, increased oxidative stress, and increased risk of diabetes and heart disease."

[circular]

Also, I typed TOMM40 in the search bar at Promethease, and the first red box I got was for rs1260326(T,T). It states nothing about AD, but that this SNP increases risk for [higher] CRP. I found it interesting as my latest hs-CRP is elevated at 7.6. Anybody know anything about this one and/or have the same variant?

Hi Ganesh, I too am T,T. My regular CRP is considered normal. I just drew blood this morning to include hsCRP. Please ping me if I forget to come back and post it. Then we'll look at our little n=2.