APOE status unknown and too scared to check

[NF52]

Hello again! I know this seems a bit out of the blue, but I'd really like to thank you again, Nancy. This reply of yours really got me out of a real anxiety funk a bit ago and everytime I circle back to this topic, I come back to this and always come away feeling better.
I thought recently how the article about Cortexyme (or Quince's, not really sure how to refer to it) study and how the author said that virtually 100% of Alzheimer's patients have an active P. Gingivalis infection and wondered what the people here thought about the validity of that statement because it just seems blatantly incorrect and doesn't sit right with me. I know elderly people who have gotten Alzheimer's and took perfectly fine care of their teeth, and elderly people who didn't that are just as sharp as ever!
The sentiment that most worried me was how the author said that PG invades your brain over "several decades", as I have had problems with my gums since I was about 8 and and 18 I still don't have sufficient funds to get it properly taken care of, was never taken to the dentist, and won't be able to for quite a while. It had me thinking I had sealed my fate at an early age and I'd start losing my memories by my mid-sixties! And that fear is still present, but lesser so.
I know that because I'm young, I take as good care of my teeth as I can at home, my oral health has greatly improved, and that I will see a dentist as soon as I can afford the care, I'll be just fine.

Hi Lila,

You are already thinking like a scientist, and questioning statements that don't "sit right" with you, and knowing that a statement that virtually 100% of people with Alzheimer's have periodontal disease doesn't seem trustworthy. Using your own experience to say "That doesn't sit right with me" is exactly how some great discoveries in Alzheimer's research have happened.

Here's some more ways to think like a scientist, since I've been lucky for the last 7 years to sit on panels with very smart Ph.Ds who research all sorts of possible causes and treatments for Alzheimer's: If something seems like it's unlikely, it's almost certainly unlikely--or due to multiple different reasons.

Here's some examples: If I said almost all people with Alzheimer's have facial wrinkles and grey or white hair (even if they color it), you would know that is related to being older, and not the cause of Alzheimer's. So unless scientists look not JUST at people with Alzheimer's, but a representative sample of people living in a community who are similar in many ways (age, race/ethnicity, gender, sexual orientation, level of education, access to health care) they can't answer the question: "Is there a difference in the statistically significant risk of periodontal disease in people who go on to develop Alzheimer's--not simply those with Alzheimer's who may have dropped off in dental care?"

The closest I've seen to an answer is that for people who are already elderly (over 65) and who have current (not young adult) periodontal disease, that MAY be an early sign of future cognitive changes, for reasons not yet understood--but only by a slightly bigger risk. My two copies of ApoE 4 are WAY more of a risk than that, and I'm still doing fine!

Another way scientists look at research claims is to say "Who benefits from this research, or this claim?" Is this a company selling a product or looking for funding to study a problem that say affects almost 100% of the people? " It's fine for researchers to seek funding, but the ones I've seen that get approved are VERY careful to make very specific claims, and usually those are backed up by specific, well-designed preliminary studies. Cortexyme failed that test, which I think is one reason the research on that is now focused in different directions.

I heard a top researcher at the Alzheimer's conference last month say we need to be learn what factors might make specific brain immune cells (microglia) either ramp up for signs of inflammation ( a good thing potentially) or lose their oomph and shut down. Figuring out how to get our immune systems to recognize and deal with any kind of bacteria or virus or toxin is now a hot topic of research. That means it's likely to be solved way before you hit 40, much less 60!

I'm sorry that you haven't been able to see a dentist yet. I wonder if you have asked at school if there are any dentists in your areas that provide a "sliding fee scale" that would cost you not too much for at least an initial teeth cleaning and a look at your gums by a dentist. If you live anywhere near a university that has a dental school, they are likely to have a free or low-cost dental clinic where dental students practice their skills. The same is true for schools for dental hygienists.

Here's a resource that may be helpful from the American Dental Association:
7 ways to find free or low-cost dental care. One of the resources is this : "

A Federally Qualified Health Center (FQHC) can provide dental services for you or your family, regardless of your ability to pay. Services are offered on a sliding scale based on your income. Many people living in rural areas, or other communities where dental services are hard to find, depend on FQHCs for regular dental care. Use this search tool to find the FQHC closest to you: https://findahealthcenter.hrsa.gov

It sounds like you're doing a great job with your teeth and dental health. Those spots by your lower teeth will not be doing ANYTHING to hurt your remarkable brain, Lila!

Nancy

[Lilac]

Thanks again for the speedy reply!
Another thing occurred to me just now, the study I linked to was published on a website about investing in stocks related to medicine! Of course the author wants his reader to believe this gingipain inhibitor is a magical cure all, it's a out money.
Unfortunately for the people out there whose lives are really affected by Alzheimer's, this is seemingly the case a lot of the time.

[Lilac]

Hello again! I know this seems a bit out of the blue, but I'd really like to thank you again, Nancy. This reply of yours really got me out of a real anxiety funk a bit ago and everytime I circle back to this topic, I come back to this and always come away feeling better.
I thought recently how the article about Cortexyme (or Quince's, not really sure how to refer to it) study and how the author said that virtually 100% of Alzheimer's patients have an active P. Gingivalis infection and wondered what the people here thought about the validity of that statement because it just seems blatantly incorrect and doesn't sit right with me. I know elderly people who have gotten Alzheimer's and took perfectly fine care of their teeth, and elderly people who didn't that are just as sharp as ever!
The sentiment that most worried me was how the author said that PG invades your brain over "several decades", as I have had problems with my gums since I was about 8 and and 18 I still don't have sufficient funds to get it properly taken care of, was never taken to the dentist, and won't be able to for quite a while. It had me thinking I had sealed my fate at an early age and I'd start losing my memories by my mid-sixties! And that fear is still present, but lesser so.
I know that because I'm young, I take as good care of my teeth as I can at home, my oral health has greatly improved, and that I will see a dentist as soon as I can afford the care, I'll be just fine.

Hi Lila,

You are already thinking like a scientist, and questioning statements that don't "sit right" with you, and knowing that a statement that virtually 100% of people with Alzheimer's have periodontal disease doesn't seem trustworthy. Using your own experience to say "That doesn't sit right with me" is exactly how some great discoveries in Alzheimer's research have happened.

Here's some more ways to think like a scientist, since I've been lucky for the last 7 years to sit on panels with very smart Ph.Ds who research all sorts of possible causes and treatments for Alzheimer's: If something seems like it's unlikely, it's almost certainly unlikely--or due to multiple different reasons.

Here's some examples: If I said almost all people with Alzheimer's have facial wrinkles and grey or white hair (even if they color it), you would know that is related to being older, and not the cause of Alzheimer's. So unless scientists look not JUST at people with Alzheimer's, but a representative sample of people living in a community who are similar in many ways (age, race/ethnicity, gender, sexual orientation, level of education, access to health care) they can't answer the question: "Is there a difference in the statistically significant risk of periodontal disease in people who go on to develop Alzheimer's--not simply those with Alzheimer's who may have dropped off in dental care?"

The closest I've seen to an answer is that for people who are already elderly (over 65) and who have current (not young adult) periodontal disease, that MAY be an early sign of future cognitive changes, for reasons not yet understood--but only by a slightly bigger risk. My two copies of ApoE 4 are WAY more of a risk than that, and I'm still doing fine!

Another way scientists look at research claims is to say "Who benefits from this research, or this claim?" Is this a company selling a product or looking for funding to study a problem that say affects almost 100% of the people? " It's fine for researchers to seek funding, but the ones I've seen that get approved are VERY careful to make very specific claims, and usually those are backed up by specific, well-designed preliminary studies. Cortexyme failed that test, which I think is one reason the research on that is now focused in different directions.

I heard a top researcher at the Alzheimer's conference last month say we need to be learn what factors might make specific brain immune cells (microglia) either ramp up for signs of inflammation ( a good thing potentially) or lose their oomph and shut down. Figuring out how to get our immune systems to recognize and deal with any kind of bacteria or virus or toxin is now a hot topic of research. That means it's likely to be solved way before you hit 40, much less 60!

I'm sorry that you haven't been able to see a dentist yet. I wonder if you have asked at school if there are any dentists in your areas that provide a "sliding fee scale" that would cost you not too much for at least an initial teeth cleaning and a look at your gums by a dentist. If you live anywhere near a university that has a dental school, they are likely to have a free or low-cost dental clinic where dental students practice their skills. The same is true for schools for dental hygienists.

Here's a resource that may be helpful from the American Dental Association:
7 ways to find free or low-cost dental care. One of the resources is this : "

A Federally Qualified Health Center (FQHC) can provide dental services for you or your family, regardless of your ability to pay. Services are offered on a sliding scale based on your income. Many people living in rural areas, or other communities where dental services are hard to find, depend on FQHCs for regular dental care. Use this search tool to find the FQHC closest to you: https://findahealthcenter.hrsa.gov

It sounds like you're doing a great job with your teeth and dental health. Those spots by your lower teeth will not be doing ANYTHING to hurt your remarkable brain, Lila!

Nancy

Hello, again
Once I start to really think about it and use the knowledge I have from personal experience and the research I've done, the inflammation thing really starts to make the most sense to me like you suggested!
I think the P. Gingivalis/periodontal disease risk factor thing is definitely most likely valid and holds some weight, but that the bacteria and it's virulence factors is just one of the many things that can cause/contribute to neuroinflammation and the reason it can appear to some researchers like it's the answer to the cause of Alzheimer's is because peridontitis is so common! And Apoe4 plays some part in that too, most likely, making it easier for the bacteria to get into the brain and eat away at the tissue. But, of course, this is just my best guess and I'm no scientist.
This then lead me to think about how resilient our brains are, and how with proper treatment and lifestyle changes, the brain can bounce back.
This is just the more positive spin I put on my hypochondriac thoughts and I'm happy that you and everyone else in this forum helped me come to this conclusion.
Food for thought! (Pun intended)

[NF52]

Hi Lila,
...
I heard a top researcher at the Alzheimer's conference last month say we need to be learn what factors might make specific brain immune cells (microglia) either ramp up for signs of inflammation ( a good thing potentially) or lose their oomph and shut down. Figuring out how to get our immune systems to recognize and deal with any kind of bacteria or virus or toxin is now a hot topic of research. That means it's likely to be solved way before you hit 40, much less 60!

Nancy

Hello, again
Once I start to really think about it and use the knowledge I have from personal experience and the research I've done, the inflammation thing really starts to make the most sense to me like you suggested!
I think the P. Gingivalis/periodontal disease risk factor thing is definitely most likely valid and holds some weight, but that the bacteria and it's virulence factors is just one of the many things that can cause/contribute to neuroinflammation and the reason it can appear to some researchers like it's the answer to the cause of Alzheimer's is because peridontitis is so common! And Apoe4 plays some part in that too, most likely, making it easier for the bacteria to get into the brain and eat away at the tissue. But, of course, this is just my best guess and I'm no scientist.
This then lead me to think about how resilient our brains are, and how with proper treatment and lifestyle changes, the brain can bounce back.
This is just the more positive spin I put on my hypochondriac thoughts and I'm happy that you and everyone else in this forum helped me come to this conclusion.
Food for thought! (Pun intended)

Lila,

I think your scientific reasoning using personal experience and research is superb. Every "hypothesis" a researcher seeks to prove or disprove is their best guess based on the evidence. Our brains are built to be resilient, with more backup systems that the NASA Space Station, and we can adapt throughout our lives. I love that you've challenged your thoughts to this new view; we're just here to applaud you!

And this is the kind of great "food" for thought I can enjoy all day!

Nancy

[Lilac]

Hi Lila,
...
I heard a top researcher at the Alzheimer's conference last month say we need to be learn what factors might make specific brain immune cells (microglia) either ramp up for signs of inflammation ( a good thing potentially) or lose their oomph and shut down. Figuring out how to get our immune systems to recognize and deal with any kind of bacteria or virus or toxin is now a hot topic of research. That means it's likely to be solved way before you hit 40, much less 60!

Nancy

Hello, again
Once I start to really think about it and use the knowledge I have from personal experience and the research I've done, the inflammation thing really starts to make the most sense to me like you suggested!
I think the P. Gingivalis/periodontal disease risk factor thing is definitely most likely valid and holds some weight, but that the bacteria and it's virulence factors is just one of the many things that can cause/contribute to neuroinflammation and the reason it can appear to some researchers like it's the answer to the cause of Alzheimer's is because peridontitis is so common! And Apoe4 plays some part in that too, most likely, making it easier for the bacteria to get into the brain and eat away at the tissue. But, of course, this is just my best guess and I'm no scientist.
This then lead me to think about how resilient our brains are, and how with proper treatment and lifestyle changes, the brain can bounce back.
This is just the more positive spin I put on my hypochondriac thoughts and I'm happy that you and everyone else in this forum helped me come to this conclusion.
Food for thought! (Pun intended)

Lila,

I think your scientific reasoning using personal experience and research is superb. Every "hypothesis" a researcher seeks to prove or disprove is their best guess based on the evidence. Our brains are built to be resilient, with more backup systems that the NASA Space Station, and we can adapt throughout our lives. I love that you've challenged your thoughts to this new view; we're just here to applaud you!

And this is the kind of great "food" for thought I can enjoy all day!

Nancy

Hi, again!
Since you've always gotten back to me relatively quickly in the past, and with very helpful and anxiety calming info. I thought I'd give this a shot. Although it's not directly about the APOE gene, it still ties into AD.
I recently discovered that variants of the PSEN gene can cause both early onset Alzheimer's and hidradenitis suppurativa which is a skin condition I have. As I've said, there's no history of Alzheimer's of any kind in my family, but I am pretty sure I inherited my skin condition from my mother so there may be a variation of the gene. And then we throw my gum disease into the mix.
Do you know anything about this? I know early onset and late onset AD are two different things, but I very rarely get straight answers from anywhere else but this forum. Sorry if I'm pestering, I just have nowhere else to go to talk about this.

[NF52]

Hi, again!
Since you've always gotten back to me relatively quickly in the past, and with very helpful and anxiety calming info. I thought I'd give this a shot. Although it's not directly about the APOE gene, it still ties into AD.
I recently discovered that variants of the PSEN gene can cause both early onset Alzheimer's and hidradenitis suppurativa which is a skin condition I have. As I've said, there's no history of Alzheimer's of any kind in my family, but I am pretty sure I inherited my skin condition from my mother so there may be a variation of the gene. And then we throw my gum disease into the mix.
Do you know anything about this? I know early onset and late onset AD are two different things, but I very rarely get straight answers from anywhere else but this forum. Sorry if I'm pestering, I just have nowhere else to go to talk about this.

You are absolutely not pestering, Lila!! The mosquitos who like to bite me when I try to weed in our messy garden are pestering me; you are asking great questions that make me learn new things--including about hidradenitis suppurativa. That's a mouthful to pronounce and sounds like a royal pain to have to live with! I hope you have a family doctor or maybe even access to a low-cost dermatologist who could help with this, because it sounds like it can get more active after puberty or around the time of your periods. You've probably already found great resources, but here's one I found that offered some possible remedies. Cleveland Clinic: Hidradenitis Suppurativa

If this is a diagnosis a doctor has given you, it may be "sporadic" (i.e. you're the only one in your family to have it) or "familial" (some, but not all family members have it). As an aside, if you've figured you must have this because of symptoms you have, it seems possible that hormonal changes and environmental reactions may be mimicking H.S., just in case that's a possibility. From one source I saw, H.S. is only seen in about 0.04% of people; about 4 in 100. Sometimes it's a pain to be unique!

You are right that some recent gene studies found SOME people with H.S. had some PSEN-1 or PSEN-2 variants, but most people didn't. In this research published in 2022, the GSC variants included PSEN and other non-PSEN genes

The largest multicenter study in cases of predominantly Caucasian ethnicity identified pathogenic GSC variation in only 12 out of 188 (6.4%) patients with HS, of which 51% had fHS [familialHS](Duchatelet et al., 2020). Smaller scale cohort studies in the United Kingdom revealed no GSC pathogenic variants in HS patients irrespective of family history of the disease

The Genomic Architecture of Hidradenitis Suppurativa—A Systematic Review I have a good friend whose large extended family of ancestors all came from a small town in Eastern Europe, where marriage among 2nd or 3rd or 4th cousins was common. People with the same last name as her maiden name are known to be more likely to have Early Onset Alzheimer's due to a PSEN mutation. But she and her immediate family (parents, siblings) don't have that, even with ApoE 4. She got tested for PSEN and is in the clear. With all that family "baggage" she's fine and in her 70's. So with no AD in your family, you can put PSEN and other early onset genes in the "discard/don't worry pile."

Enjoy fall, Lila, and rest easy. Your brain and your genes are resilient and wonderful!

Nancy

[Lilac]

Hi, again!
Since you've always gotten back to me relatively quickly in the past, and with very helpful and anxiety calming info. I thought I'd give this a shot. Although it's not directly about the APOE gene, it still ties into AD.
I recently discovered that variants of the PSEN gene can cause both early onset Alzheimer's and hidradenitis suppurativa which is a skin condition I have. As I've said, there's no history of Alzheimer's of any kind in my family, but I am pretty sure I inherited my skin condition from my mother so there may be a variation of the gene. And then we throw my gum disease into the mix.
Do you know anything about this? I know early onset and late onset AD are two different things, but I very rarely get straight answers from anywhere else but this forum. Sorry if I'm pestering, I just have nowhere else to go to talk about this.

You are absolutely not pestering, Lila!! The mosquitos who like to bite me when I try to weed in our messy garden are pestering me; you are asking great questions that make me learn new things--including about hidradenitis suppurativa. That's a mouthful to pronounce and sounds like a royal pain to have to live with! I hope you have a family doctor or maybe even access to a low-cost dermatologist who could help with this, because it sounds like it can get more active after puberty or around the time of your periods. You've probably already found great resources, but here's one I found that offered some possible remedies. Cleveland Clinic: Hidradenitis Suppurativa

If this is a diagnosis a doctor has given you, it may be "sporadic" (i.e. you're the only one in your family to have it) or "familial" (some, but not all family members have it). As an aside, if you've figured you must have this because of symptoms you have, it seems possible that hormonal changes and environmental reactions may be mimicking H.S., just in case that's a possibility. From one source I saw, H.S. is only seen in about 0.04% of people; about 4 in 100. Sometimes it's a pain to be unique!

You are right that some recent gene studies found SOME people with H.S. had some PSEN-1 or PSEN-2 variants, but most people didn't. In this research published in 2022, the GSC variants included PSEN and other non-PSEN genes

The largest multicenter study in cases of predominantly Caucasian ethnicity identified pathogenic GSC variation in only 12 out of 188 (6.4%) patients with HS, of which 51% had fHS [familialHS](Duchatelet et al., 2020). Smaller scale cohort studies in the United Kingdom revealed no GSC pathogenic variants in HS patients irrespective of family history of the disease

The Genomic Architecture of Hidradenitis Suppurativa—A Systematic Review I have a good friend whose large extended family of ancestors all came from a small town in Eastern Europe, where marriage among 2nd or 3rd or 4th cousins was common. People with the same last name as her maiden name are known to be more likely to have Early Onset Alzheimer's due to a PSEN mutation. But she and her immediate family (parents, siblings) don't have that, even with ApoE 4. She got tested for PSEN and is in the clear. With all that family "baggage" she's fine and in her 70's. So with no AD in your family, you can put PSEN and other early onset genes in the "discard/don't worry pile."

Enjoy fall, Lila, and rest easy. Your brain and your genes are resilient and wonderful!

Nancy

Thank you again for a speedy and informative
reply!
I was just very unsettled and disoriented by all the information flying at me. I found that mutation of the PSEN gene can cause both familial early onset AD and familial HS, but not ever, at least in any significant amount, both diseases in the same person. They are 2 different things. But some sources were telling me it was still possible I have the genes for familial EOFAD because my HS is, indeed, familial. But, with no family history of either early or late onset Alzheimer's, I'm sure I have nothing to worry about. Plenty of people have familial HS (and periodontal disease as well, since that was my original concern in all of this) and are well into middle aged with no cognitive decline.

[NF52]

Thank you again for a speedy and informative
reply!
I was just very unsettled and disoriented by all the information flying at me. I found that mutation of the PSEN gene can cause both familial early onset AD and familial HS, but not ever, at least in any significant amount, both diseases in the same person. They are 2 different things. But some sources were telling me it was still possible I have the genes for familial EOFAD because my HS is, indeed, familial. But, with no family history of either early or late onset Alzheimer's, I'm sure I have nothing to worry about. Plenty of people have familial HS (and periodontal disease as well, since that was my original concern in all of this) and are well into middle aged with no cognitive decline.

You’ve done a great job of sleuthing on this, and given the evidence of both your family’s history of no Alzheimer’s and your finding that it’s extremely rare (somewhere between zero and 6% maybe) that people would have both PSEN and HS, you can happily assume that your ancestors did not give you both. Whew!!!

I wonder if the next time you worry about a possible connection with Alzheimer’s, you can use the technique of self-talk to view it as a researcher would, as a statistical question and look for reasons why you would not have the risky gene? It might be a way to acknowledge the uncertainty of life, and still feel that optimism is a valid choice. But you’re always welcome to ask questions here!!

Nancy