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You can follow someone who is Apoe4 and taking Rapamycin under the care of Dr Green on this forum for AD prevention:
https://www.apoe4.info/forums/viewtopic.php?f=2&t=6057&hilit=Rapamycin
Apoe4 was first discovered as associated with CVD, and AD more recently. There’s a dearth of studies linking cerebral vascular dysfunction, Apoe4, and AD (hundreds+). Apoe4 is not a single causative AD gene...only a component of a much larger polygenic and epigenetic driven neurological disease. Apoe4 is enriched in AD, with 2/3 of AD persons having a least one Apoe4 allele; although, 4/4 homozygotes have far higher risk hazard ratio for AD. Rapamycin targets mTOR (1and 2), and down regulates fundamental nutrient sensing pathways associated with aging. Rapamycin has to be taken intermittently so as not to turn off mTOR2, critical immune system function. Use with extreme care. There are new rapalogs under development that target mTOR1 and leave mTOR2 alone, but not commercially available that I am aware.
some reference papers:
https://www.ncbi.nlm.nih.gov/m/pubmed/31586989/?i=8&from=rapalogs
https://www.ncbi.nlm.nih.gov/m/pubmed/30034573/?i=35&from=rapalogs
https://www.ncbi.nlm.nih.gov/m/pubmed/31324799/?i=14&from=rapalogs
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Thank you for your prompt reply. It is very much appreciated.
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Jonathan Horwitz APOE4 is not such a concern to males according to Stanford research. I don't have a link handy but you can surely find it with a search, a few years ago a met analysis was done going over existing research and found that if you correlate against sex that the observed pathologies only applied to females. I haven't kept up on this so there may be some updates, however when I discussed it with my genetics counselor she knew about the study and was not concerned (for me).
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Dan Very interesting, Dan. It struck me that a genetics counselor should be part of the medical team of modern medicine. Strange-21st century and physicians are too busy treating sick and dying people to prevent disease in healthy patients.
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That is very interesting. I recently called one of the genetics counselors at INVITAE ( one of the largest genetics testing labs in the US ) to ask if they do APOE4 testing. She replied that they no longer do the tests as the results are not individually predictable. By that she meant that when they were doing the tests they found that they had patients with APOE2/2 with Alzheimer's and "elderly" APOE4/4 patients with no signs of cognitive decline and therefore they could no longer give patients accurate predictive advice. So they have stopped doing the tests until other factors are established that would give a more meaningful predictive diagnosis.
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I find the lab comment on termination of APOE reporting very odd. As of time of writing, APOE is still the #1 risk gene "associated" with risk of AD. Even though, depending on your ancestry, percentage of persons with APOE4 can vary between < 5% (Sardinians) to near 40% (African tribes), yet, in AD, 2/3 of persons are APOE4+...clearly, there is a massive enrichment of APOE4 "associated" with AD, but not singularly causative.
https://sci-hub.tw/10.1080/03014460600594513
https://onlinelibrary.wiley.com/doi/epdf/10.1046/j.1469-1809.1999.6340301.x
And yes, there is no one who can tell you that you will or will not get AD based on your APOE status. And AD is just one type of dementia (the most common) on a spectrum of dementias.
https://www.alzheimers.net/resources/types-of-dementia/
Family AD history, especially maternal history, greatly amplifies risk regardless of APOE status or sex. Getting AD is a complex polygenic and epigenetic outcome with many different pathways leading to ultimate synaptic loss. The only thing I agree with the lab on is yes, your APOE status does not confer prognosis...epigenetics is a massive contributor. There are very few diseases that are singularly genetic causative (that we know of).
But APOE has far ranging systemic effects (periphery and CNS), and knowing your APOE status can help you make lifestyle interventions to counteract the WELL KNOWN impact of APOE on these systems.
https://en.wikipedia.org/wiki/Apolipoprotein_E#cite_note-Farrer1997-59
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509527/
I am 55yr old APOE3/4 male, mom has late onset AD. Finding out I was APOE3/4 3 yrs ago was the best thing that ever happened to me. I radically changed my lifestyle for the better! From diet, fasting protocols, exercise, meds, baselining my brain, both anatomically (imaging) and neurocognitively, I have undergone massive, positive health changes that I believe has pushed out all cause mortality (not just a singular original focus on AD). All stemming from a single APOE result.
The lab reply is completely non-sensical, and frankly a failure of service!
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Thank you for your reply. It makes a lot of sense. As an additional example of lab reporting, 23 and me also does not report APOE4 status. It is possible, however, to use their raw data to get a result but it is extremely difficult and the average person would not bother.
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Jonathan Horwitz
23andme doesn't actually formally report...they give you the SNP alleles and you can confirm APOE status. Is that what you meant by your INVTAE post...they didn’t actually formally report APOE status? Once you know your reported alleles, it’s very simple:
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Thank you for your help.
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Does Prometheus give APOE status?
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Randall James
https://www.snpedia.com/index.php/Promethease
I checked my Promothease report (from 23andme upload), it calls out specifically the two SNP's, and you still have to make the specific APOE determination.
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Quest labs has the ApoE genetic test, I order it in my office and the cash price for the test is just under $100 (the benefit of ordering it as a cash price is that it is not submitted to insurance and excluded from your medical records as a potential "preexisting condition" with your insurer).
I had the pleasure of meeting Dr Green last week and was impressed with his clinical experience of Rapamycin to treat cognitive decline.
ApoE 3/4 and 4/4 carriers express features of dysfunctional lipid metabolism and are predisposed to insulin resistance. mTOR inhibition is an excellent strategy to mitigate insulin resistance. Ideally, keep HOMA-IR <1.0, this becomes harder to achieve with calorie restriction/fasting as we age.
