Promotor Region - rs405509

Insights and discussion from the cutting edge with reference to journal articles and other research papers.
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Max100
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Promotor Region - rs405509

Post by Max100 »

Long time reader, first time poster. Thanks everyone here for the insight and helping decipher some of these studies.

I’ve read several studies about rs405509 and it’s potential protective (GG) or detrimental (TT) effects.

I’m a TT, so was curious if there research that says your Alzheimer’s risk is X% more likely with Apoe4?

I’ve also noticed that there’s disagreement that these promoter genes are additive and that they are like a package deal with Apoe4. Studies mention that the G allele is “highly underrepresented” for E4 and the T allele the same with E2. Basically, most E4 have a T or two and most E2 have only G. There’s also studies that say this may be more of an additional risk factor for non-Apoe4 carriers.

Anyone have data or insight into rs405509? Many thanks in advance for feedback!
Attabeth
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Re: Promotor Region - rs405509

Post by Attabeth »

Max100 wrote: Wed Aug 31, 2022 9:13 am Long time reader, first time poster. Thanks everyone here for the insight and helping decipher some of these studies.

I’ve read several studies about rs405509 and it’s potential protective (GG) or detrimental (TT) effects.

I’m a TT, so was curious if there research that says your Alzheimer’s risk is X% more likely with Apoe4?

I’ve also noticed that there’s disagreement that these promoter genes are additive and that they are like a package deal with Apoe4. Studies mention that the G allele is “highly underrepresented” for E4 and the T allele the same with E2. Basically, most E4 have a T or two and most E2 have only G. There’s also studies that say this may be more of an additional risk factor for non-Apoe4 carriers.

Anyone have data or insight into rs405509? Many thanks in advance for feedback!
Hi Max100, great to hear from you. I'm sure someone will be providing you with some feedback and answers to your questions. As a welcome intern, I wanted to welcome you and make sure you were familiar with the site. If you are a long time reader you may already be familiar with the Primer. It includes researched-based prevention strategies.

Some helpful tips and tricks to navigate the site include the How-to Guide. This guide is a great resource I found helpful when I started posting. It includes topics such as navigating the forum, private messaging, and searching. One great tip is using the quote (") button when replying to a post. Using the button will automatically alert the member of your response. It really helps to keep the conversation going.

If you would like to tell us more about yourself or interested in learning more about other members check out Our Stories.

It looks like you are exploring this subject thoroughly and learning all you can to keep yourself healthy. I hope this site is helpful to you and I look forward to hearing more from you in the future. Thanks again for reaching out as I'm sure someone will chime in with some insights for you soon.

Be well,
Beth
NF52
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Re: Promotor Region - rs405509

Post by NF52 »

Max100 wrote: Wed Aug 31, 2022 9:13 am Long time reader, first time poster. Thanks everyone here for the insight and helping decipher some of these studies.

I’ve read several studies about rs405509 and it’s potential protective (GG) or detrimental (TT) effects.

I’m a TT, so was curious if there research that says your Alzheimer’s risk is X% more likely with Apoe4?

I’ve also noticed that there’s disagreement that these promoter genes are additive and that they are like a package deal with Apoe4. Studies mention that the G allele is “highly underrepresented” for E4 and the T allele the same with E2. Basically, most E4 have a T or two and most E2 have only G. There’s also studies that say this may be more of an additional risk factor for non-Apoe4 carriers.

Anyone have data or insight into rs405509? Many thanks in advance for feedback!
Hi Max100,

Thanks for being both a long-time reader and first-time poster: Your question is, as researchers like to say ,"a great question!" Probably as-yet uncertain answers. It seems like that's because these single nucleotide variants (SNVs) generally don't have the clear ApoE4 profile of Big Ben over London for late-life Alzheimer's risk. So you get the kind of results you've mentioned, with data analysis from the large, long-running Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort suggesting rs405509 adds some risk to those WITHOUT ApoE4, but not to those WITH ApoE4.

Given that ApoE4 itself has all sorts of effects on lipids, the heart and brain, I thought this March 22 article might be of interest. Its dietary recommendation is consistent with what most of us try to do anyway:
In the quote: SFA= saturated fats; TC=Total Cholesterol.
rs405509 TT, APOA1 rs670 G, ABCA1 rs2230806 CC and LIPC rs1800588 TT might benefit from a diet low in SFA to maintain healthy TC, LDL-c and HDL-c levels.
Personalized Dietary Recommendations Based on Lipid-Related Genetic Variants: A Systematic Review

This article is dense, but the conclusion from studying rs405509 and other variants seems that any changes caused by the variants don't affect the all-important brain connectivity in healthy people with ApoE4.
In conclusion, our study did not detect any changes in structural brain networks that would imply alterations in the integration and segregation of structural network properties in cognitively healthy individuals with different risk factors. We identified the right paracentral lobule as a hub brain area in high-risk individuals, but not in low-risk individuals. A longitudinal study of the same cohort with the incorporation of functional neuroimaging data could evaluate this phenotype further.
Dementia Risk Factors Modify Hubs but Leave Other Connectivity Measures Unchanged in Asymptomatic Individuals: A Graph Theoretical Analysis

I heard at the Alzheimer's Association's International Conference recently that lifestyle, especially moderate exercise and overall good metabolic health can especially benefit those of us with ApoE4 genetic risk. So I choose not to worry about this one SNP!

Keep posting; you have lots of knowledge to share!
4/4 and still an optimist!
Max100
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Re: Promotor Region - rs405509

Post by Max100 »

NF52 wrote: Wed Aug 31, 2022 6:20 pm
Max100 wrote: Wed Aug 31, 2022 9:13 am Long time reader, first time poster. Thanks everyone here for the insight and helping decipher some of these studies.

I’ve read several studies about rs405509 and it’s potential protective (GG) or detrimental (TT) effects.

I’m a TT, so was curious if there research that says your Alzheimer’s risk is X% more likely with Apoe4?

I’ve also noticed that there’s disagreement that these promoter genes are additive and that they are like a package deal with Apoe4. Studies mention that the G allele is “highly underrepresented” for E4 and the T allele the same with E2. Basically, most E4 have a T or two and most E2 have only G. There’s also studies that say this may be more of an additional risk factor for non-Apoe4 carriers.

Anyone have data or insight into rs405509? Many thanks in advance for feedback!
Hi Max100,

Thanks for being both a long-time reader and first-time poster: Your question is as researcher like to say "a great question" with probably as-yet uncertain answers. It seems like that's because these single nucleotide variants (SNVs) generally don't have the clear Big Ben over London profile that ApoE4 has shown and so you get the kind of results you've mentioned, with it seeming in studies of the large and long-running Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, that it adds some risk to those with ApoE4 4, but not to those with it.

Given that ApoE4 itself has all sorts of effects on lipids, the heart and brain, I thought this March 22 article might be of interest for its dietary recommendation, which seems overall consistent with what most of us try to do anyway:
In the quote: SFA= saturated fats; TC=Total Cholesterol.
rs405509 TT, APOA1 rs670 G, ABCA1 rs2230806 CC and LIPC rs1800588 TT might benefit from a diet low in SFA to maintain healthy TC, LDL-c and HDL-c levels.
Personalized Dietary Recommendations Based on Lipid-Related Genetic Variants: A Systematic Review

And while most of this abstract is above my comprehension, the conclusion from studying rs405509 and other. variants seem to be saying these variants do cause some changes, but those don't affect the all-important brain connectivity in healthy people with ApoE4.
In conclusion, our study did not detect any changes in structural brain networks that would imply alterations in the integration and segregation of structural network properties in cognitively healthy individuals with different risk factors. We identified the right paracentral lobule as a hub brain area in high-risk individuals, but not in low-risk individuals. A longitudinal study of the same cohort with the incorporation of functional neuroimaging data could evaluate this phenotype further.
Dementia Risk Factors Modify Hubs but Leave Other Connectivity Measures Unchanged in Asymptomatic Individuals: A Graph Theoretical Analysis

Given the recent consensus I heard at the Alzheimer's Association's International Conference that lifestyle DOES play a large role in modulation genetic risk, and that other factors (diabetes maybe chief among them) increase risk, along with vascular health and systemic inflammation, I choose not to worry about this SNP!

Keep posting; you have lots of knowledge to share!
NF52,

Thanks for the feedback, links and perspective. Doesn’t sound like something I should be overly concerned with. I did see a list posted from several years ago that had SNP’s in order of importance and weight as related to LOAD. One list that could confer increased risk and another with decreased. I didn’t catch rs405509 or others in the “promotor region” listed. Thank you again!
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