TREM4 & APOE4

[Terancewilliams2019]

Hi, Anyone here got both? Is it common?

Had severe anxiety since my Father passed with Dementia back in September convincing myself that I could see many of the symptoms which he had in myself, decided to take the leap of faith and undertake a 23&me to see if I was at increased risk and bang APOE4/4. Was obviously a shock but sort of got used to that but then decided to dig further with Genetic Risk Assessment in the hope I could find some protective genes but no bang bang now have TREM4 which seems to be just as bad.

My Mother passed real young so no idea whether she would have got dementia.

Started to review Bresden online and offers some hope but noticed it is very focused on APOE4, would it have any merit on someone with TREM4 as well?

Many thanks

[Jenny B]

Hi, Anyone here got both? Is it common?

Had severe anxiety since my Father passed with Dementia back in September convincing myself that I could see many of the symptoms which he had in myself, decided to take the leap of faith and undertake a 23&me to see if I was at increased risk and bang APOE4/4. Was obviously a shock but sort of got used to that but then decided to dig further with Genetic Risk Assessment in the hope I could find some protective genes but no bang bang now have TREM4 which seems to be just as bad.

My Mother passed real young so no idea whether she would have got dementia.

Started to review Bresden online and offers some hope but noticed it is very focused on APOE4, would it have any merit on someone with TREM4 as well?

Many thanks

First I'd like to say welcome to our very informative and resourceful community, Terancewilliams! There are many who love to dig for answers here and I am one of them. I would also like to say I can appreciate the anxiety you must be feeling at this time. My dad passed earlier this year from Lewy Body Dementia and I have found the support and understanding of these like minded people invaluable. If there are answers out there, this forum will do their very best to find them which helps to reduce the anxiety from the unknown.
I am not familiar with this genetic variant so I went to our WIKI Link and down to related genes where I found information on Trem2 in the Alzepedia. In the description of TREM2 (haven't found anything on TREM4), this stood out to me as a partial answer to your question " Preliminary evidence suggests that TREM2 may affect AD pathogenesis via amyloid-related neuroinflammation and via phagocytosis of amyloid and neuronal debris." A quick perusal of a lot of scientific information indicates to me that it may interfere in the clean up of plaques and reducing inflammation. I'm excited to see who else may have insight to this genetic variant in our group.

Therefore, since the goals of the Bredesen Protocol include reducing inflammation throughout the body and in the brain specifically, I believe following this lifestyle would be of benefit. In fact, as a naturopathic doc I have learned that efforts to reduce inflammation is of benefit to all of us regardless of our genetics, especially in these chronically stressful time. I've recently been learning how stress itself is quite inflammatory for the brain. The protocol is an effort in clean up, detoxification, nutrient support and overall optimization of brain health and the health of your WHOLE self.

There is a lot of reason for hope to be found here and I'd like to direct you to one great resource, the Primer written by a doctor who is herself, ApoE 4/4. It is an introduction to ApoE4 and possible prevention strategies. Also, the How-To Guide can help you navigate the ApoE4.info website.
Hope to chat with you soon again.

Warm regards,

Jenny BC

[NF52]

Hi, Anyone here got both? Is it common?

Had severe anxiety since my Father passed with Dementia back in September convincing myself that I could see many of the symptoms which he had in myself, decided to take the leap of faith and undertake a 23&me to see if I was at increased risk and bang APOE4/4. Was obviously a shock but sort of got used to that but then decided to dig further with Genetic Risk Assessment in the hope I could find some protective genes but no bang bang now have TREM4 which seems to be just as bad.

My Mother passed real young so no idea whether she would have got dementia.

Started to review Bresden online and offers some hope but noticed it is very focused on APOE4, would it have any merit on someone with TREM4 as well?

Many thanks

Welcome, Terancewilliams2019,

First, let me give you a virtual hug and my deep sympathy on the loss of your father in September and your mother much too soon. I think your father would be proud to know that you took a "leap of faith" to see what you could do to support your own brain health.

So while I am not an Alzheimer's researcher, I also have ApoE 4/4 and a family history of early strokes, heart disease and late-life Alzheimer's and vascular dementia. And yet I see hope for the future of you and me!! At age 68 I have no heart disease nor do my 3 siblings or all but one of my 20 cousins and no cases of young onset Alzheimer's. As someone who has been involved in clinical trials for healthy people with ApoE 4/4 and 3/4, I can tell you that many 1000's of people like you and me are walking around with healthy brains!

Scientists now realize that Alzheimer's is not a simple, single disease, any more than heart disease or cancer are simple. Our brains do best when we avoid getting severe brain injuries in accidents, when we avoid diabetes that can starve them of energy, and when we keep our hearts healthy. it also helps if we have lives that keep us busy in something we enjoy doing, if we can make a good night's sleep a priority, and if we eat healthy food most of the time. You and your father likely had very different lives from childhood on, so you can have very different paths for your "healthspan" and lifespan.


One final thought on TREM4: It can be VERY confusing to figure out exactly where the research is on some new discoveries--and to find if you have the actual risk genes! For example, TREM2 is a known risk gene, but only a small percentage of people have the specific "alleles" (variations) that seem to cause a risk of late life Alzheimer's, and it's not clear if that risk is any different, or added to, the risk of ApoE 4/4. But I haven't seen the same risk for TREM4, so I'm not sure that you should worry at all about that.
Here's an explanation from Snpedia about of how one little letter can make a big difference in TREM2: snpedia:rs75932628

If you feel comfortable posting the SNPs that worry you, folks on this forum may be able to share their experiences with that.

Please know, Terance, that we have had that same deep anxiety that you have felt this year. It does get better with time, and with your own belief that you have overcome other challenges and can this one. I like the Stoics view that we cannot control the outcome of any journey; we can control how we prepare for it and try to experience each day as one good part of that journey.

[Terancewilliams2019]

Thanks very much for the responses, I will see if i can access to the raw data and see if in fact I am worrying about nothing in relation to TREM4. It would be a huge relief if that was the case

Quick question, I have long suspected my Dad has Lewy Body rather than normal Alz due to issues with nightmares and acting out dreams, the Neurologist who cared for the father towards the end was almost certain LBD due to this specific symptom.

Is there anything I could have done to help someone with LBD rather than ALz? Does the Bresden protocol still apply? Or if I am at in fact at increased risk for LBD due to my father having this particular condition.

Best Regards,

[NF52]

...
Quick question, I have long suspected my Dad has Lewy Body rather than normal Alz due to issues with nightmares and acting out dreams, the Neurologist who cared for the father towards the end was almost certain LBD due to this specific symptom.

Is there anything I could have done to help someone with LBD rather than ALz? Does the Bresden protocol still apply? Or if I am at in fact at increased risk for LBD due to my father having this particular condition.
Best Regards,

Hello again,

I'm so sorry that your dad suffered from nightmares and acting out of dreams (sometimes called Sleep Behavior Disorder), which is a clinical indication of possible Lewy Body disease (LBD) or what is sometimes called DLB (Dementia with Lewy Bodies). To my knowledge, the Bredesen protocol was not developed for, or widely tested on, people with LBD. The regions of the brain affected by LBD are different than those in Alzheimer's, and memory and language tend to be less affected early, with more symptoms of motor problems (gait, balance, etc) and behaviors or changes in personality. The toxic amyloid beta plaques and tau tangles seen in Alzheimer's patients, especially in the frontal and temporal lobes, are not seen in "pure" LBD. Instead it appears to be a different mis-folded protein called alpha-synuclein (a-synuclein for short).

Researchers are learning more about LBD, including this from the Lewy Body Dementia Associationwebsite:

Dementia with Lewy Bodies
DLB is the second most common form of degenerative dementia in the elderly next to Alzheimer’s disease (AD). Recent estimates suggest that DLB represents 4 to 16% of cases of dementia seen in the clinic, but the true prevalence is probably higher. The most common features of DLB are progressive cognitive impairment leading eventually to full-blown dementia, parkinsonian motor symptoms (tremor, slowed mobility, stiffness of muscles, stooped posture, shuffling gait), visual hallucinations, and fluctuations in levels of alertness and cognitive acuity. Other symptoms include acting out dreams (REM sleep behavior disorder) and disturbances of autonomic function (low blood pressure, constipation and urinary frequency). Severe sensitivity or over-reaction to antipsychotic drugs (aka neuroleptics) are also common.
... Diagnosis is challenging because the order of symptom appearance, their relative severity and the combination of features present varies among individuals....
The cause of LBD is unknown. Brain pathological changes in LBD involve selective damage and loss of nerve cells in certain regions of the brain (example: substantia nigra in the brainstem). Affected, but less damaged cells contain Lewy bodies, which are a microscopic aggregation of a specific protein (α-synuclein). The Lewy body is the pathological signature of LBD that overwhelms the cell’s normal biological functions and causes it to die. There are many possible causes of LBD but researchers are just beginning to understand the reasons why some people are more susceptible to developing LBD.

So I think the answer you would get from researchers is that given our current knowledge, neither you nor his doctors could have prevented your father's LBD. Your love and concern was the best gift you could have given him during his difficult journey.

As for your own risk, remember that you only have 50% of his DNA and a completely different health history. Whatever caused his brain's a-synuclein protein to misfold and become toxic may be absent in you. It does seem that some very recent research is beginning to look at how ApoE 4 may "dial down" methylation of some genes in the brain, possibly contributing to, not directly causing, a risk of DLB or AD in ApoE 4 carriers. You may want to read the very new Wiki section on methylation by our Senior Contributor Support Staff Susan J here: Methylation Full disclosure: This is a deep dive into science-heavy topics!

At the end of the day, the strategies recommended in the Primer are likely to be very useful for you regardless of your specific genetic profile. (And as someone with ApoE 3/4, you may be eligible for clinical trials yourself when you're 50 or older. You can see more about patient registries enrolling people who are interested in online monitoring here:Gene Match, APT WEBSTUDY and the NIH program All of Us

Warm wishes for good health and some joy this holiday season, Terance, from a "sister" ApoE 4/4!