23 and Me Kit Information

[WillsMeme]

Does anyone have any more info on the TOMM40 gene and ApoE4 gene together? I read that Takeda and Zinfandel have abandoned the TOMMORROW study. I was screened for the study and actually have a letter saying I am at LOW risk for MCI, although I was accepted into the A4 study because I am at HIGH risk (4/3 + PET scan positive for amyloid buildup). I assume that means I don’t have the problematic TOMM40, but I’m going to get a Promethease report to be sure. Is there anything else I should look for in the Promethease report? Thanks.

[NF52]

Does anyone have any more info on the TOMM40 gene and ApoE4 gene together? I read that Takeda and Zinfandel have abandoned the TOMMORROW study. I was screened for the study and actually have a letter saying I am at LOW risk for MCI, although I was accepted into the A4 study because I am at HIGH risk (4/3 + PET scan positive for amyloid buildup). I assume that means I don’t have the problematic TOMM40, but I’m going to get a Promethease report to be sure. Is there anything else I should look for in the Promethease report? Thanks.

Hi WillsMeme,
It's always disappointing when a drug trial is stopped; this time is was for what is called "inadequate treatment effect" in an "interim futility analysis". In plain English that means that if outside evaluators determine that there is no way to reach the desired outcome in the time left, then there's no point continuing the study.
The Tommorrow study screened about 25,000 people to enroll about 3500 who had both at least one copy of ApoE 4 and the TOMM 40 gene, based on an earlier study that such people would progress faster to MCI. People who progress faster to MCI might be a good group to study because if a drug works, you might have more people in the placebo group who progress to MCI than those in thee intervention group over 5 years. In the article below from Alz.Forum, this was seen as problematic for two reasons:
1) the assumption of added risk from TOMM40 plus ApoE 4 is "controversial", meaning not consistently found.
2) the only outcome measure was a diagnosis of MCI; most studies now look at cognitive changes, changes in amyloid (for anti-amyloid drugs) and other biomarkers. So they set themselves a target that may be years out.

Unlike other current prevention trials, TOMMORROW did not test an anti-amyloid therapy. Pioglitazone and related compounds such as rosiglitazone are diabetes drugs that had been abandoned for symptomatic AD treatment based on negative trials, although they did appear to improve brain metabolism, which falters in early AD (Dec 2002 webinar; Sep 2010 news; Dec 2012 news). ..TOMMORROW’s outcome measure diverged from those of other ongoing prevention trials in that it used time to progression to MCI-AD, rather than measuring cognitive decline. “[That] is a tough [outcome] to achieve and usually requires a lot more power. All of the other prevention trials use a sensitive global cognitive measure with a continuous score, or a combination of a cognitive measure and progression to MCI

There's no Tomorrow for Tommorrow

The good news is that they plan to share their data at the July AAIC conference in Chicago, and other scientists may learn from that.

I would say you don't have to worry about the TOMM40. And I would be careful to interpret results from Promethease with some caution. A study that tells you that you have 1.6x the risk of some condition is not useful if you don't know the original odds. For example, my son was born with a congenital (not genetic) anomaly that is seen in 1 out of every 4500 births. If I were to increase those odds by 60% it would still be a very small risk.

Hope your experience in the A4 study is positive; that study has already led to lots of published papers and good information for scientists to use in other trials.

[Roamingseer]

NF52, thank you very much for that post. Like Shirley, I have the rs2075650(G,G) and was concerned that my 2.5x risk (3/4) had now become 10X. Another point about these studies, it would be helpful if there was an available description on APOE4.INF on how to interpret the statistical information (OR, CI, P, SF) and how to interpret these values, or how to access how reliable the study is. Thank you again.

[WillsMeme]

My daughter just got her 23 and Me results. She is 4/4, which was a shock to me since I’m 4/3 (her dad died at 50 but one of his sisters has LOAD). She was more shocked that she has 0.2% sub-Saharan African genes. She’s 45 so has a long time to practice good habits. I guess that means both of her kids are at least 4/ something. They will realize that some day when they are older.

[NF52]

Hi WillsMeme,
Your daughter's dad must have had at least one ApoE 4 allele. The good news is that she has you to bounce her reactions off as she processes this, and you can encourage her to explore this site and Dr. Bredesen's book and other resources. Like her, I got a report that I am 0.2% sub-Saharan African. It was more a cool surprise than a shock. Given the influence of Arabic (Moorish) culture in Spain and Italy and the trade as far away as Ireland with Rome, it seems pretty likely to me that we all have much more of a genetic mix that we think! That's a good thing for the species I think!.