13 ms·

Right on the heals of the recent publication that shows that beta-amyloid in the brain specifically wraps around HerpesViral particles in order to prevent them

Right on the heals of the recent publication that shows that beta-amyloid in the brain specifically wraps around HerpesViral particles in order to prevent them from spreading! https://www.cell.com/neuron/fulltext/S0896-6273(18)30526-9 https://www.cell.com/neuron/fulltext/S0896-6273(18)30526-9 Turns out, a great many viruses use low-density-lipoproteins (LDLs, of heart disease fame) to travel around the body, and some even enter our cells by binding to LDL receptors. The APOE gene, associated with alzheimers, binds and transports herpes in the brain and hepatitis viruses in the liver! https://medium.com/@InfinoMe/cholesterol-have-we-shot-the-messenger-a3f5dfeba09 https://medium.com/@InfinoMe/cholesterol-have-we-shot-the-me...

api 8y ago
Umm... sooo... Alzheimers might be viral? Or is it just common mechanisms that might be at work?
- Shank 8y ago
  After reading a bit about it, I think the hypothesis is more that Alzheimer’s is the side effect of the body’s own anti-viral systems acting to contain viruses in the brain. Most of the latest studies are showing a reduction in Alzheimer’s risk after treating patients who have some form of herpes with anti-viral medication.
  - Beefin 8y ago
    Correct, as humans evolved, parasitic infections increased. The APOE gene was a method of slowing down or stopping parastic infection to the brain. "Among the Tsimane as a whole, adults with APOE4 got poorer scores in these tests. But when the team focused on the people with high parasite levels, they saw that the APOE4 carriers had better mental skills, even outperforming APOE3 carriers who were parasite-free." https://www.theatlantic.com/science/archive/2017/01/why-does-a-gene-that-increases-alzheimers-risk-still-exist/512396/ https://www.theatlantic.com/science/archive/2017/01/why-does...
    - subcosmos 8y ago
      No.... APOE is a lipoprotein that transports cholesterol, and viruses jump onto it to get into cells. Amyloid-Beta is what seems to be wrapping around the virus particles to block their transit.
- subcosmos 8y ago
  Heart disease might be partly viral as well! Evidence going back to the 80's shows this.
  - scentoni 8y ago
    https://www.webmd.com/oral-health/features/healthy-teeth-healthy-heart https://www.webmd.com/oral-health/features/healthy-teeth-hea...
- tyu100 8y ago
  No. The beta amyloid protein is the primary 'cause' of Alzheimer's. It builds up in the brain and kills neurons and synapses. Tens of billions of dollars have been spent developing drugs to reduce the amount of amyloid in the brain to try and combat Alzheimer's, none of which has led to an effective treatment. This newer theory is that the cause of the amyloid build-up is an immune response to the herpes virus increasingly infiltrating the brain (as you get older the blood/brain barrier that protects your brain from infections weakens) so a possible treatment is to try and reduce the levels of herpes infection rather than attacking the amyloid protein which is your body's immune response to the herpes infection. The APOE4 gene is infamous for increasing amyloid production and being a major risk factor for early-onset Alzheimers and so carriers of the gene are often used in studies to see the effect of treatments. (@subcosmos below has a good explanation of what this gene actually does)
  - subcosmos 8y ago
    The thing about viral infections of the nervous system is that you don't even need to consider the blood brain barrier. Viruses travel backwards through neurons by hijacking microtubule transport networks, and many groups have hypothesized in the literature that it could be getting into the brain by simply infecting a peripheral nerve and traveling up the spinal chord.
    - dnautics 8y ago
      > Viruses travel backwards through neurons by hijacking microtubule transport networks, How does this help crossing the BBB? Can you give a citation?
      - subcosmos 8y ago
        Check out Figure 1 in this paper. The model effectively is that HSV infects a great many people in early life, and becomes latent in neurons until old age. Then it suddenly wakes up again and travels to the brain. All it takes is an infected muscle or other tissue, allowing the virus to get into the nerve. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546524/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546524/ Some VERY notable statistics mentioned in the paper : "Such studies have revealed endemic infection rates of 31% in children aged 6–14, rising to 49% in adults aged 14–49, and to a high of 80–90% in the population over 65. In one study of 40 autopsied TGs, HSV-1 sequences were amplified from DNA or RNA extracted from 81% of TGs from demented subjects, and 74% of controls" I blogged about these connections here, for I think that this retrograde transport phenomenon might explain Tau phosphorylation, which is a secondary hallmark of Alzheimer's and other dementias : https://medium.com/@InfinoMe/cholesterol-have-we-shot-the-messenger-a3f5dfeba09 https://medium.com/@InfinoMe/cholesterol-have-we-shot-the-me...
tyu100 8y ago
Great links, thank you.
sctb 8y ago
Discussed here: https://news.ycombinator.com/item?id=17521994 https://news.ycombinator.com/item?id=17521994.
msla 8y ago
> Right on the heals Freudian autocorrect error!
- subcosmos 8y ago
  Hah! I've spent the last several years studying dementia at UCSF actually, and I'm well known in the building for compulsively making puns CONSTANTLY... I once told my boss, who studies sociopaths, that I have "sociopuny" ... and she facepalmed harder than you can imagine .... This one wasn't intentional. I have a problem.
  - sogen 8y ago
    I'd love to meet you next time I am in SF :D
  - sitkack 8y ago
    http://punslam.com/ http://punslam.com/
    - subcosmos 8y ago
      Ah man, everyone keeps insisting that I compete in this. Mind you, I'm not legally allowed to deploy my puns within city limits. EDIT: from the downvote, it seems that I've already been PUNished ... Do... your ... worst HN!
aaavl2821 8y ago
Very informative and thought provoking post If I understand correctly, APOE helps viruses enter neurons. How does APOE4 behave differently than other isoforms in this regard? APOE itself isn't implicated in AD risk, just the APOE4 isoform. And I couldn't tell from your post or a brief lit search, what's the current thinking on the relationship btw APOE and amyloid beta? I think APOE4 is associated with higher levels of beta amyloid but I don't know why. You mention a study showing beta amyloid traps herpes simplex? Is there a mechanism by which APOE4 drives more beta amyloid aggregation to fight viral infections, but as an unintended result leads to AD? I've briefly followed some of the recent papers on a viral link to AD but haven't spent much time on it, your post has inspired me to do some more research!
- subcosmos 8y ago
  Here are a few major points : * APO-E isoform, that predicts alzheimers risk, correlates with how much beta amyloid is present in the brain * It also correlates with how much Herpes Virus is present : https://www.theatlantic.com/science/archive/2018/07/herpes-viruses-alzheimers/564887/ https://www.theatlantic.com/science/archive/2018/07/herpes-v... "Readhead and his colleagues have shown that the more E4 copies someone has, the more HHV–6A and HHV–6B viruses they are likely to have in their brains." * We also know that if you knock APOE out in a mouse, and then infect it, there is WAY less HSV penetration in the brain (see figure 1, and note that the Y-axis is logarithmic!) : http://jvi.asm.org/content/76/23/12394.full http://jvi.asm.org/content/76/23/12394.full * Also, APOE isoforms predict whether or not Hepatitis B virus will give you liver cancer. Note that its the E3 genotype that is risky for this, yet its the E4 genotype thats bad for Alzheimers. I take this to be evidence that hepatitis viruses and herpes viruses likely have different binding affinities to these two isoforms. https://www.ncbi.nlm.nih.gov/pubmed/26823800 https://www.ncbi.nlm.nih.gov/pubmed/26823800 * Someone should do some drug screening to eliminate binding between known viral capsids and APOE variants. cough YC Bio
  - aaavl2821 8y ago
    Seems like there is still a lot to learn about the underlying biology, though very provocative findings thus far. I may be misunderstanding but I'd think that if beta amyloid traps herpes, then higher levels of beta amyloid would correlate with lower levels of virus, but it seems that isn't the case? Would antiviral therapy be more effective that blocking capsid-APOE interaction? It's my understanding that blocking protein protein interactions is challenging, although inhibiting that interaction would be a nice specific way to block the mechanism
dghughes 8y ago
And the HPV vaccine used to cure the malignant skin cancer on a 97 year-old woman recently.
- toomuchtodo 8y ago
  It should be noted that cervical cancer is of the same type as that woman’s skin cancer that was cured with direct tumor injections of Gardasil9. Further high signal discussion on Reddit that goes into more depth: https://www.reddit.com/r/science/comments/8z1lg0/hpv_vaccine_eliminates_skin_cancer_in_97yearold/ https://www.reddit.com/r/science/comments/8z1lg0/hpv_vaccine...

api 8y ago

Umm... sooo... Alzheimers might be viral? Or is it just common mechanisms that might be at work?

Shank 8y ago
After reading a bit about it, I think the hypothesis is more that Alzheimer’s is the side effect of the body’s own anti-viral systems acting to contain viruses in the brain. Most of the latest studies are showing a reduction in Alzheimer’s risk after treating patients who have some form of herpes with anti-viral medication.
- Beefin 8y ago
  Correct, as humans evolved, parasitic infections increased. The APOE gene was a method of slowing down or stopping parastic infection to the brain. "Among the Tsimane as a whole, adults with APOE4 got poorer scores in these tests. But when the team focused on the people with high parasite levels, they saw that the APOE4 carriers had better mental skills, even outperforming APOE3 carriers who were parasite-free." https://www.theatlantic.com/science/archive/2017/01/why-does-a-gene-that-increases-alzheimers-risk-still-exist/512396/ https://www.theatlantic.com/science/archive/2017/01/why-does...
  - subcosmos 8y ago
    No.... APOE is a lipoprotein that transports cholesterol, and viruses jump onto it to get into cells. Amyloid-Beta is what seems to be wrapping around the virus particles to block their transit.
subcosmos 8y ago
Heart disease might be partly viral as well! Evidence going back to the 80's shows this.
- scentoni 8y ago
  https://www.webmd.com/oral-health/features/healthy-teeth-healthy-heart https://www.webmd.com/oral-health/features/healthy-teeth-hea...
tyu100 8y ago
No. The beta amyloid protein is the primary 'cause' of Alzheimer's. It builds up in the brain and kills neurons and synapses. Tens of billions of dollars have been spent developing drugs to reduce the amount of amyloid in the brain to try and combat Alzheimer's, none of which has led to an effective treatment. This newer theory is that the cause of the amyloid build-up is an immune response to the herpes virus increasingly infiltrating the brain (as you get older the blood/brain barrier that protects your brain from infections weakens) so a possible treatment is to try and reduce the levels of herpes infection rather than attacking the amyloid protein which is your body's immune response to the herpes infection. The APOE4 gene is infamous for increasing amyloid production and being a major risk factor for early-onset Alzheimers and so carriers of the gene are often used in studies to see the effect of treatments. (@subcosmos below has a good explanation of what this gene actually does)
- subcosmos 8y ago
  The thing about viral infections of the nervous system is that you don't even need to consider the blood brain barrier. Viruses travel backwards through neurons by hijacking microtubule transport networks, and many groups have hypothesized in the literature that it could be getting into the brain by simply infecting a peripheral nerve and traveling up the spinal chord.
  - dnautics 8y ago
    > Viruses travel backwards through neurons by hijacking microtubule transport networks, How does this help crossing the BBB? Can you give a citation?
    - subcosmos 8y ago
      Check out Figure 1 in this paper. The model effectively is that HSV infects a great many people in early life, and becomes latent in neurons until old age. Then it suddenly wakes up again and travels to the brain. All it takes is an infected muscle or other tissue, allowing the virus to get into the nerve. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546524/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546524/ Some VERY notable statistics mentioned in the paper : "Such studies have revealed endemic infection rates of 31% in children aged 6–14, rising to 49% in adults aged 14–49, and to a high of 80–90% in the population over 65. In one study of 40 autopsied TGs, HSV-1 sequences were amplified from DNA or RNA extracted from 81% of TGs from demented subjects, and 74% of controls" I blogged about these connections here, for I think that this retrograde transport phenomenon might explain Tau phosphorylation, which is a secondary hallmark of Alzheimer's and other dementias : https://medium.com/@InfinoMe/cholesterol-have-we-shot-the-messenger-a3f5dfeba09 https://medium.com/@InfinoMe/cholesterol-have-we-shot-the-me...

tyu100 8y ago

Great links, thank you.

sctb 8y ago

Discussed here: https://news.ycombinator.com/item?id=17521994 https://news.ycombinator.com/item?id=17521994.

msla 8y ago

> Right on the heals Freudian autocorrect error!

subcosmos 8y ago
Hah! I've spent the last several years studying dementia at UCSF actually, and I'm well known in the building for compulsively making puns CONSTANTLY... I once told my boss, who studies sociopaths, that I have "sociopuny" ... and she facepalmed harder than you can imagine .... This one wasn't intentional. I have a problem.
- sogen 8y ago
  I'd love to meet you next time I am in SF :D
- sitkack 8y ago
  http://punslam.com/ http://punslam.com/
  - subcosmos 8y ago
    Ah man, everyone keeps insisting that I compete in this. Mind you, I'm not legally allowed to deploy my puns within city limits. EDIT: from the downvote, it seems that I've already been PUNished ... Do... your ... worst HN!

aaavl2821 8y ago

Very informative and thought provoking post If I understand correctly, APOE helps viruses enter neurons. How does APOE4 behave differently than other isoforms in this regard? APOE itself isn't implicated in AD risk, just the APOE4 isoform. And I couldn't tell from your post or a brief lit search, what's the current thinking on the relationship btw APOE and amyloid beta? I think APOE4 is associated with higher levels of beta amyloid but I don't know why. You mention a study showing beta amyloid traps herpes simplex? Is there a mechanism by which APOE4 drives more beta amyloid aggregation to fight viral infections, but as an unintended result leads to AD? I've briefly followed some of the recent papers on a viral link to AD but haven't spent much time on it, your post has inspired me to do some more research!

subcosmos 8y ago
Here are a few major points : * APO-E isoform, that predicts alzheimers risk, correlates with how much beta amyloid is present in the brain * It also correlates with how much Herpes Virus is present : https://www.theatlantic.com/science/archive/2018/07/herpes-viruses-alzheimers/564887/ https://www.theatlantic.com/science/archive/2018/07/herpes-v... "Readhead and his colleagues have shown that the more E4 copies someone has, the more HHV–6A and HHV–6B viruses they are likely to have in their brains." * We also know that if you knock APOE out in a mouse, and then infect it, there is WAY less HSV penetration in the brain (see figure 1, and note that the Y-axis is logarithmic!) : http://jvi.asm.org/content/76/23/12394.full http://jvi.asm.org/content/76/23/12394.full * Also, APOE isoforms predict whether or not Hepatitis B virus will give you liver cancer. Note that its the E3 genotype that is risky for this, yet its the E4 genotype thats bad for Alzheimers. I take this to be evidence that hepatitis viruses and herpes viruses likely have different binding affinities to these two isoforms. https://www.ncbi.nlm.nih.gov/pubmed/26823800 https://www.ncbi.nlm.nih.gov/pubmed/26823800 * Someone should do some drug screening to eliminate binding between known viral capsids and APOE variants. cough YC Bio
- aaavl2821 8y ago
  Seems like there is still a lot to learn about the underlying biology, though very provocative findings thus far. I may be misunderstanding but I'd think that if beta amyloid traps herpes, then higher levels of beta amyloid would correlate with lower levels of virus, but it seems that isn't the case? Would antiviral therapy be more effective that blocking capsid-APOE interaction? It's my understanding that blocking protein protein interactions is challenging, although inhibiting that interaction would be a nice specific way to block the mechanism

dghughes 8y ago

And the HPV vaccine used to cure the malignant skin cancer on a 97 year-old woman recently.

toomuchtodo 8y ago
It should be noted that cervical cancer is of the same type as that woman’s skin cancer that was cured with direct tumor injections of Gardasil9. Further high signal discussion on Reddit that goes into more depth: https://www.reddit.com/r/science/comments/8z1lg0/hpv_vaccine_eliminates_skin_cancer_in_97yearold/ https://www.reddit.com/r/science/comments/8z1lg0/hpv_vaccine...