t_rubi wrote:Wow, so it sounds like 4/4 is indeed quite rare. Since my first post I have read a bit more about expected progress in therapies, and you're right, it is very encouraging! Thanks for the responses.
As someone twice your age with ApoE 4/4, I just want to reassure you that while rare-ish (geneticists don't view things as rare unless they are in far fewer than 1% of the population), ApoE 4/4 is also not something that means your future is written in stone. Here's a link to a snpedia page on the rs429358 allele you wondered about.https://www.snpedia.com/index.php/Rs429358
It does indicate that it is one of the markers for ApoE 4.
But at the same time, it's a great example of how crowd-sourced information isn't always either current or accurate. For example, the text of snpedia asserts that this raises your risk of Alzheimer's by 12x ! That's absurd for several reasons. Here's just a couple:
*The average risk of either Mild Cognitive Impairment (MCI) or dementia of any type for people with ApoE 3/3 (75% of people with European ancestry) is estimated at 10-15% by the age of 85. So 12 x 10 = 120% risk??
* The study that "found" that statistic was done in England based on "42 case-control series published before July 1996"! That means these were people diagnosed with Alzheimer's before MRI and other imaging tests were available, and who were referred to a particular study center for examination. Not a study that followed a population over time and determined who got Alzheimer's. More recent studies of "diagnosed" AD cases using post-mortem brain studies have estimated that 30% of those diagnosed with AD did NOT have the disease.
Note: Actual likely risk: A 2017 meta-analysis on far more recent population-based incidence, showed that people with ApoE 4/4 who are in my age range and older (60-75 years), have a 30-55% risk statistically of eitther MCI or AD by the age of 85.APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts
That's important, since we have a lot of "mileage" on our brains, so anyone younger than us has much more ability to influence their risk.
So first piece of advice: read everything on ApoE 4/4 "risk" with a dose of skepticism.
Second piece of advice: Take great comfort in the fact that you are 33! Regardless of the general impression that "no progress has been made" in studying Alzheimer's in the last 20 years, that's simply not true. It's now known to be a highly complex disease, with multiple layers of pathology, and multiple lifestyle factors that can move the needle on risk. (The Primer is a great source for more on those.)
Alzheimer's research is happening as every great university and research center in the world--not just in pharmaceutical companies. I got to meet in December with lots of Ph.D's a few years older than you who are working on cutting edge research funded by government grants. One of them, who had multiple relatives with Alzheimer's told me that he was confident that by the time people his age needed it (say by the age of 50) it would be possible to give personalized recommendations to people based on a sophisticated understanding of who was at risk from tau, who from amyloid, who from inflammation, who from insulin resistance, who from vascular issues, etc. etc. By identifying people with high risk early, they would be able to be monitored and given appropriate recommendations and interventions long before their brains were damaged.
And as long as there are people twice your age who have ApoE 4/4 who are doing fine, you should feel confident that you will also--with some good decisions that you are already making!