Using human brain tissue in lab, researchers show herpes link to Alzheimer’s | Hacker News Reader

Using human brain tissue in lab, researchers show herpes link to Alzheimer’s

statnews.com

255 pointsvo2maxer121 comments

Here's the original publication. The paper is actually more focused on the 3d engineered brain model and is titled "A 3d human brain-like tissue model of herpes-induced Alzheimer's disease":

https://advances.sciencemag.org/content/6/19/eaay8828

The publication actually seems to highlight the demonstration of the 3d brain Alzheimers model as more of what the accomplishment of the paper is (as compared to a demonstration of a herpes/Alzheimers link). Studying Alzheimer's is really difficult because the mouse models etc that we have today are particularly poor for this disease case, which means we can barely rely on any preclinical work done in these models in determing whether or not a drug is going to work in clinical trials. Better models to study Alzheimer's will be very important in fighting the disease. For more publications on the 3d model, here is what the paper cited in its methods section for how they made the brain-like structures:

https://www.sciencedirect.com/science/article/pii/S221367111...

https://www.nature.com/articles/nprot.2015.091

This is good because it helps continue to break down the whole "amyloid hypothesis" stanglehold on Alzheimer's research and we might finally start seeing some progress.

This is not the whole story, but it's a ray of sunshine to get medical scientists moving in a another direction.

Question is what two generations of amyloid experts will do with their careers once it is seen that amyloids are just a response to a problem, not the problem. Discover new prions, maybe?

But the first priority has to be to get the purse strings and publication barriers out of the hands of amyloid partisans. Anybody deep in amyloids will have some time to find another gig, because the whole Amyloid Industrial Complex will take an appalling length of time to dismantle. Peer reviewed publication and grants are profoundly conservative, with only very occasional exceptions.

Thanks for linking that, the first thing I wondered when they said "herpes" was "which one"?

Looks like the answer to that is herpes simplex virus type I (HSV-1)

the statnews article says that too

Also relevant:

> “Active [herpes] infection may not be a requirement for Alzheimer’s disease,” Kaplan and his colleagues wrote. A history of herpes infection might be “sufficient to initiate Alzheimer’s.”

> But not in everyone. An estimated two-thirds of people 50 and younger are infected with HSV-1. Although nothing close to that number will develop Alzheimer’s from a virus or anything else, scientists aren’t sure what combination of genetics, lifestyle, and other factors determines who will.

HSV always seemed particularly poorly understood in the society to me, e.g. with many people getting it as children due to careless parents/extended family, and the benign branding of "cold sore" as if it is related to a cold. Given that the vaccine for 1 or 2 has proved to be extremely challenging, always wondered if the public simply being more well-informed on this topic could help reduce the incidence in the population.

Asymptomatic shedding of HSV has to be considered, too. "Transmission commonly occurs from contact with an infected partner who does not have visible lesions and who may not know that he or she is infected. In persons with asymptomatic HSV-2 infections, genital HSV shedding occurs on 10.2% of days, compared to 20.1% of days among those with symptomatic infections." (https://www.cdc.gov/std/herpes/stdfact-herpes-detailed.htm)

It's called Herpese Simplex.. but there's nothing simple about it!

Future Man reference.

https://www.imdb.com/title/tt4975856/

> e.g. with many people getting it as children due to careless parents/extended family

Puhleeze. HSV is present in the majority of the population. Branding parents as "careless" because their children get it is ridiculous.

Not letting family members kiss your kids on the mouth and not letting your kids use other people's cups/forks etc? If the entire population did this there would be fewer herpes infections.

edit: the downvotes are interesting. If I had made the statement "We can take steps to reduce COVID-19 transmission" I can't imagine I'd get the same result. I can only assume that people really are ashamed of having herpes and are reacting emotionally.

If you can figure out a way to get a 3 year old to care about what utensils they use or who's cake they finish, you're probably on track to solve even bigger problems than this!

You can't prevent 100% of infections. We could do a whole lot better than we're doing now. Getting rid of the moniker "cold sore" would be a great start.

What's your gameplan for the rest of your life? You're never going to kiss anyone or share a cup or a smoke or any of the thousands of ways that have infected the vast majority of humanity? You can even get it passing through your mom's birth canal.

Your two examples of transmission are so specific that I'm not sure you know how it spreads. Just extended family members kissing or sharing cups with your kids? What?

Herpes-1 is just part of the human condition. Time to get over it. Btw, odds are that you have it. And for your own sanity, don't worry -- it doesn't mean you were making out with your family nor their kids.

I'm in the second half of my life and I married an HSV-negative. I try not to put my mouth on sketchy things.

You both got blood tests for both types of HSV before you were married I assume?

You "married an HSV-negative"? Quite the romantic.

>You're never going to kiss anyone or share a cup or a smoke or any of the thousands of ways that have infected the vast majority of humanity?

Sounds reasonable

I am 30 and have never kissed anyone, and no plans to change that soon. Although I had some shared cups. I probably should get tested. But there is a good change I have avoided all herpes, even EBV. I hope they can find a vaccine soon.

Never change, HN

If we all stopped having sex, that would admittedly solve the issue of all disease rather thoroughly. No people, no human Herpes infections.

If we all had fewer sex partners, that would go a long way.

I mean, yeah, I guess if we avoid all physical contacts during our entire life until the world pop drops to 0 we could get rid of herpes. /s

Herpes-2 is also part of the human condition at this point

Either way, they are gross

The rate of infection is 90% worldwide.[1] It's not just careless parents and lack of awareness, it's endemic to all of mankind.

Given that asymptomatic shedding occurs there's basically no way to not transmit herpes to your partner. Unless we remove kissing from our social norms, it's going to stick around.

[1]https://en.wikipedia.org/wiki/Epidemiology_of_herpes_simplex

> careless parents/extended family

> benign branding of "cold sore"

This is a dangerous, hurtful opinion and you need to be downvoted. No one is to be shamed for this virus.

A third of teenagers will acquire HSV-1 during childhood from simply putting things into their mouths. There is no way to prevent this sort of transmission. [1]

Most of the world's population has the virus. [2] Given these odds, you probably have the virus yourself and may or may not be asymptomatic.

The focus should be on finding a cure, not changing social norms or shaming people. The stigma is obstructing our focus. It's also impeding research, which as it may turn out, is a cause for Alzheimer's and related neurodegenerative disorders.

So much suffering from something that isn't anyone's fault, yet everyone blames "bad parenting" and "sexual promiscuity" for. It's shameful and we need to do better.

[1] https://www.cdc.gov/nchs/products/databriefs/db304.htm

[2] https://www.who.int/news-room/fact-sheets/detail/herpes-simp...

On the other hand...https://lee-phillips.org/isrealPediatrics/

Well, it's good to see they're slowly modernizing this, but in the end it's still a pretty bizarre practice even if you don't do it in that particularly disgusting way.

Not an American, and always wondered how it somehow became the standard in America....

It by "it" you mean circumcision, it was thought to be good for hygiene. But these days it is no longer routine, as it was a few decades ago.

Even though I don't agree with this person, I think labeling what they said as "dangerous" is silly. Who exactly is in danger?

The statement "There is no way to prevent this sort of transmission" while linking CDC data that shows changes in the trend of transmission over time are at odds to me.

There are most definitely ways to reduce spread.

>The focus should be on finding a cure, not changing social norms or shaming people.

There is no cure yet, thus changing habits and social norms is our only chance at reducing this problem outside experts who are working on the problem directly.

I don't know whether or not labeling parents as villains has anything to do with what needs to be done to label and reduce spread; but I dare say that the attitude of "Nothing to be done, let's give up due to the fact that the virus is prevalent." is in fact the dangerous opinion for society at large.

>... and you need to be downvoted.

The call to arms for down-voting a comment you disagree is a tactic that I personally feel is cheap and a disgusting misuse of the karma/discourse system that is in place.

syntactically speaking reduce spread is statistical while prevent transmission is individual. There is no preventing transmission with 100% surety no matter how careful and good of a parent you are, so saying bad parenting might be a bit much.

I totally agree that too many people are downvoting just because they don't like what someone has to say even though what was said falls within general parameters of acceptable social discourse, or even worse when the downvoted has the temerity to disagree with the downvoter.

So I guess I'll go upvote to fix the karmic scales.

Yeah, shaming is counterproductive. But I have to disagree with one of your points: changing social norms.

Changing social norms can be have huge benefits. Very timely example is that social norms are likely a major reason so many Asian countries have much lower Covid-19 infection rates than western countries. If only Americans could get over themselves and stop shaking hands and wearing their shoes in the house. I say that as an American expat.

... Americans wear their shoes in the house? I'm a (non-white) American and this is news to me. Whenever someone comes to my house, or I go to someone else's house, people leave their shoes at the door. I thought this was something that pretty much everyone from every part of the world did.

Is it a regional thing? Because I grew up in Southern California and lived there many years. Also lived in Arizona and northern California for a few years. Always shoes in the house everywhere I went and everyone I knew.

I definitely think it's regional. I think that it's more common in very dry climates like california/arizona. I mean honestly, my shoes are almost never visibly dirty when entering the house. It's not like there's mud everywhere in southern california. I wear shoes in the house all the time and my carpet looks fine. Until covid-19 I never thought twice about it.

I think you're right about the regional thing, although when you think about it wearing the shoes in the house is a pretty weird thing to do. Probably also not good for foot/ankle development given all the support most shoes give you.

Most definitely not. It depends on the household or how clean inside is itself. Usually you tell by context or just knowing the person whose house you're entering.

Personally here in Michigan at my house right outside Detroit shoes are taken off if you are going inside to stay. If you're grilling or doing yardwork or moving from the front to the back (no path but thru house currently) they stay on. I'd never keep them on for longer than 10 minutes inside but it's common.

My cousin's is totally different. Shoes off before you hit the carpet. Maybe cause they keep it obsessively clean? Carry them to the backdoor if you have to. It's not something I even think about - they just come off, I don't need his wife upset or anything.

Calif. resident born and raised. Shoes off. However feet are covered with slipper or sandle indoors always. Many homes in ca are built on concrete slabs so walking indoors barefoot isn’t all that comfortable in feet, knees or ankles. Having a barrier between the bottom of your feet and the foundation absorbs and reduces some of this hardness. But outside shoes are for outside only. We have always thought of it like walking in your cleaned laundry. Would you do that... no so why would you consider wearing dirty shoes on clean flooring. Everything, including ourselves are often on our floors so keep them as clean as possible.

A lot of Europeans, too. Usually when I have a lot of guests I'll tell them they can leave the shoes on. I'll just wash the carpets afterwards and clean the house anyway.

If it's only a few friends I usually ask them to take their shoes off.

But I know many people who always wear shoes inside. I think it's also due to the cold. In Northern Europe you don't want to walk around barefoot, so keeping on the shoes is comfortable.

It is seen in American movies all the time, people jumping on the sofa/bed with their shoes on.

Big if true! This would mean that just as the Gardasil 9 vaccine prevents HPV, which leads to almost all forms of cervical cancer [1] (as well as others), a vaccine for HSV-1 might prevent someone from developing Alzheimer's later in life.

There are HSV-2 vaccines in clinical trials [2], but I'm unaware of any HSV-1 vaccines as far along. Please chime in if you are aware!

[1] https://www.nccc-online.org/hpvcervical-cancer/cervical-canc...

[2] https://clinicaltrials.gov/ct2/show/NCT04222985

This paper only shows that brain-like lab grown tissue develops Amyloid-beta plaques (known to occur in patients with AD) to combat mircobial i.e. viral attack.

There are a low of assumptions here: (1) Organoid tissue represents human-brain. Human (and mammalian) brain is a much more complex entity to be even remotely similar to this. (2) We do not know how amyloid-beta plaques are related to Alzheimer's Disease (AD) i.e. whether they are the cause of AD or a symptom that occurs when one has AD. All we know is the existence of these plauqes can occur before the symptoms of AD are seen (even upto 30 years before you are diagnoised with AD). Whether removal of plaques makes you AD free is a mystery. (3) HSV/Herpes virus might not be the only cause of formation of amyloid plauqes. There are tons of other microbial infections that have been shown to cause increase of plaques.

But more research into the microbial theory of AD is definitely something that would shed more light on the interplay between microbes and the brain.

All true, correlation does not equal causation, but it's still fun to speculate when it looks like there might be a relatively inexpensive path (ie a vaccine we're going to develop anyway) to success.

It is fun indeed to speculate that. One could even use this line of "imagination" to get big Pharma interested in investing in this line of fundamental research which, as we have been reminded more recently, is extremely crucial.

I tend to feel like "fun speculation" around new science research feeds loads of incorrect information being spread. Which makes it not fun to me at all.

If you're getting your health information solely from Hacker News, without any additional research or critical thinking, you should probably not do that. I'm not a domain expert (Virologist or otherwise in medicine), nor do I pretend to be, and I qualified my statement at the top of the thread ("might"). Everything else in my comment was factual.

I just don’t think wild speculation about science is fun. What is fun to me about science is fact based exploration. Hypothesis is great and conjecture has its place, but wild conjecture is not fun to me. You can feel otherwise and that’s okay!

I don't believe my original comment was wild conjecture (although it did lack a citation how I arrived at the hypothesis), but in keeping with your ideals as it relates to putting forth a thesis in a public forum:

> We believe that HSV1 is a major contributory factor for Alzheimer’s disease and that it enters the brains of elderly people as their immune system declines with age. It then establishes a latent (dormant) infection, from which it is reactivated by events such as stress, a reduced immune system and brain inflammation induced by infection by other microbes.

> Excitingly, successful prevention of Alzheimer’s disease by use of specific anti-herpes agents has now been demonstrated in a large-scale population study in Taiwan. Hopefully, information in other countries, if available, will yield similar results.

https://theconversation.com/alzheimers-disease-mounting-evid... (Alzheimer’s disease: mounting evidence that herpes virus is a cause)

The author of the post is Ruth Itzhaki, Professor Emeritus of Molecular Neurobiology, University of Manchester

This (in my opinion) would lead a reasonable person to believe that an HSV-1 vaccine would prevent the onset of Alzheimer’s (through the prevention of an HSV-1 infection), in a similar fashion to how the HPV vaccine prevents (among other cancers) cervical cancer. I hope you have found some value in this subthread.

Ah, you're probably right. I'm sorry, I believe I misunderstood. Well it would be great to figure out a vaccine for HSV-1 and HSV-2.

No apologies necessary, I frequently forget that I can’t assume context is known and should be providing more citations upfront.

There is correlation between zoster vaccine and herpes simplex.

This has correlation to lesser the outbreaks or make them stop altogether. I can attest to that.

This is what some specialist doctors recommend for patient with bad herpes outbreaks.

I guess this would be already good starting point.

Example source (pdf): https://proceedings.med.ucla.edu/wp-content/uploads/2016/03/...

Have you intentionally exposed yourself to your previous triggers (assuming you had them)?

How long has it been since you had the zoster vaccine?

Were you of an on-label age for the zoster vaccine at receipt or was it off-label usage? Put another way did you receive Varivax or Zostavax dosing and were you in the on-label group (1-50 for Varivax and 50+ for Zostavax)?

The data isn't great but there's a fair bit of anecdata as you report and in your link that suggests there might be some protection against HSV from the VZV vaccines, possibly based on genetics or age of recipients.

Also your link was broken for me but the below might work.

https://proceedings.med.ucla.edu/index.php/2016/03/10/varice...

I've had outbreaks but they were way less severe after that.

I'm under 30. This recommendation came from doctor who specializes in herpes. She did warn me it might not work, but she has seen overall good results -outbreaks are less severe, rarer, or dissapear altogether.

I think it's been around five years.

There was a paper also on that, but couldn't find.

Thank you for the reply - I last looked into it for someone before the UCLA article came out and their doctor wasn't convinced by the French study but also wasn't completely against it. The person opted to not get the vaccine at that time. More and more it seems like the potential benefit is worth any side effects.

I'm I EU if that matters and as far as I know, I have no sideffects. I was supposed to be healthy for both shots, that was the only requirement.

Why I'm sharing this information usually, because there are people out for who herpes is not annoyance but life disrupting virus. They often do not even know that there are antiviral drugs out there that work really well. They do think that there isn't much to do other than to suffer because when they were young or had bad doctor who said "oh everyone has it". My hope is maybe some people might go back to their doctor and say "please, it's disrupts my life" and they get appropriate treatment.

Given the extremely high rates of HSV-1 infection (roughly half of everyone 14-49 and more among older people [0]), I'm guessing that it would be difficult to eradicate it using a vaccine (although I'm certainly not an expert).

As a side note, the HPV vaccine only protects against strains 16 and 18 (with some also providing protection against types 6 and 11). That covers the majority of the strains that cause cancer, but it certainly doesn't prevent HPV infections altogether. Remember that HPV is the same virus that causes common and plantar warts as well. A Wikipedia quote: "Most people acquire genital HPV infections at some point in their lives, and about 10% of women are currently infected.[25] A large increase in the incidence of genital HPV infection occurs at the age when individuals begin to engage in sexual activity. As with cutaneous HPVs, immunity to genital HPV is believed to be specific to a specific strain of HPV."[1]

I don't think it's possible to get rid of either virus very easily, although vaccines that target the most dangerous types are a good defense.

[0] https://www.cdc.gov/nchs/products/databriefs/db304.htm [1] https://en.wikipedia.org/wiki/Human_papillomavirus_infection

> Given the extremely high rates of HSV-1 infection (roughly half of everyone 14-49 and more among older people [0]), I'm guessing that it would be difficult to eradicate it using a vaccine (although I'm certainly not an expert).

True, it'd be similar to Australia where their cervical cancer rates will decline over decades as older people die and for younger people [1], the HPV vaccine uptake rate was very high. Folks with HSV-1 are likely stuck with it for life unless CRISPR comes to the rescue.

> As a side note, the HPV vaccine only protects against strains 16 and 18 (with some also providing protection against types 6 and 11). That covers the majority of the strains that cause cancer, but it certainly doesn't prevent HPV infections altogether. Remember that HPV is the same virus that causes common and plantar warts as well.

"GARDASIL 9 is a vaccine indicated in females and males 9 through 45 years of age for the prevention of cervical, vulvar, vaginal, and anal cancers caused by human papillomavirus (HPV) Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11."

https://www.merckvaccines.com/gardasil9/

Disclaimer: I'm a male in my mid 30s who has had Gardasil 9 administered by a medical professional.

[1] https://www.theguardian.com/society/2018/oct/03/australia-on... (The Guardian: "Australia on track to wipe out cervical cancer within 20 years" [2018])

I stand corrected on the number of strands of HPV that Gardasil 9 protects against. That's more comprehensive than I remembered (and I've also received it).

Thanks for correcting me!

It was updated IIRC (I don't know if the FDA has updated the indication to follow)

Didn't they discover that periodontitis causes Alzheimer: https://advances.sciencemag.org/content/5/1/eaau3333

Perhaps any infection that reaches the brain can cause Alzheimer and amyloid-beta plaques are there to fight the infection

Came here to say this. Didn't that connection sweep through here a while back?

I just checked. Turns out the herpes connection has been made before too:

(1) Alzheimer's risk 10 times lower with herpes medication (2 years ago) https://news.ycombinator.com/item?id=17540094

(2) Some studies show an association between the herpes virus and Alzheimer’s (2 years ago) https://news.ycombinator.com/item?id=18265115

(3) Researchers Find Herpes Viruses in Brains Marked by Alzheimer's Disease (2 years ago) https://news.ycombinator.com/item?id=17366591

(4) Link Between Alzheimer’s and Herpes (2 years ago) https://news.ycombinator.com/item?id=17521994

From my skimming of the OP, which references some of this research, I think these prior findings demonstrated strong correlation, but this is the first study that demonstrates some causal relationship.

Sweet, thanks – haven't had time to even skim yet!

(1) Gum bacteria implicated in Alzheimer's and other diseases (1 year ago) https://news.ycombinator.com/item?id=19606025

(2) Gum disease–causing bacteria could spur Alzheimer’s (1 year ago) https://news.ycombinator.com/item?id=18987015

Some people propose that Alzheimer is in fact a symptom caused by a multitude of different diseases. Similar to how cancer has multiple types and causes.

Medical people mostly find the correlation unpersuasive, mostly because poor dental hygiene correlates strongly with all kinds of illnesses that break down ability to self-maintain.

I.e, it is just as likely that Alzheimer's causes periodontal complications.

That said, those bacteria do find their way to parts of the body that are protected against the immune system, and the brain would be an excellent host site.

So let me get this straight, the elevator pitch for this is:

"We're going to make a micro-brain out of dick skin and spider webs so we can give it herpes and see if it gets Alzheimers."

Just wanted to make sure.

Seems accurate! Since you read the article, the real question to me is what is the brain protecting against?

If amyloid plaques are a defense mechanism that happens to permanently block neuron function, then what happens if that the plaques don't form and the herpes infection spreads?

There doesn't have to be an answer, evolution doesn't cause improvements, people reproduce before this happens.

I wonder if people above 60 should then start taking acyclovir if the have the virus in their system, as a potential preventative? They should do a study on this.

Quick google does that’s been investigated

It looks like there are some ongoing studies:

https://www.ncbi.nlm.nih.gov/pubmed/32034019

https://www.nia.nih.gov/alzheimers/clinical-trials/valacyclo...

So according to WHO, 67% of people older than 50 have Herpes 1: https://www.who.int/en/news-room/fact-sheets/detail/herpes-s...

How do you account for the disparity between the massive infection rate and the relatively low Alzheimer's rate?

They might not be old enough for it to matter yet, and we might see numbers approaching that 67% as people live longer.

https://www.nia.nih.gov/health/what-causes-alzheimers-diseas...

"Older age does not cause Alzheimer’s, but it is the most important known risk factor for the disease. The number of people with Alzheimer’s disease doubles about every 5 years beyond age 65. About one-third of all people age 85 and older may have Alzheimer's disease." (emphasis mine)

Perhaps if we beat cancer and cardiovascular diseases etc and see human lifespans reaching 100+ years old, we'll see close to 67% of people at that age get Alzheimer's.

I don't think one should extrapolate this study on a lab-grown human-like tissue to mammals like rodents in the first place. Extrapolation to humans is even more bizzare.

Maybe it's like prostate cancer in that it changes so slowly that often something else kills you long before the prostate cancer has a chance to? [0]

[0]https://www.cancer.gov/types/prostate/understanding-prostate...

The article covers this question, they think it is just a factor. A funnel towards Alzheimer's that a lot of people still end up getting to the bottom of.

So what does this mean if you get a cold sore every year or two? You're more likely to get Alzheimer's?

It means you’re not getting enough lysine at those times.

Source on info? Can you supplement with lysine?

No (I think). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461191/

Not really efficaceous: https://www.cochrane.org/CD010095/SKIN_measures-preventing-c...

My vet said the same (chronic respiratory problems in cats are often caused by feline herpesvirus). The effect on the cat is at best slight.

Only anecdotal, but yes.

Supplement before if I know I will be increasing UV exposure. e.g. visiting high desert

Visiting know stressful environment. (choose your own adventure)

Or if I think I might be starting to feel one coming on.

Outbreaks in the decades after are way down from outbreaks from the decades before, but please do remember correlation is not causation and becoming a person who can consider mitigation may be more significant then the particular ritual.

Oh and prescription anti-virals work wonders.

I'm not sure if anecdotes are allowed or welcomed, hope this is okay: Around 2003 I learnt about lysine having something to do with preventing HSV-1, so I got some and took some large doses until the bottle was finished. Haven't had a cold sore since, and I was getting them ~yearly before. Sometimes I can feel the tingling and think shiiit, here it comes again finally, but I never really had a proper breakout.

Also, the more I hear about the HSV/Alzheimer's link, the more I freak out about my shitty memory :(

> Sometimes I can feel the tingling

That's the viral shedding.

Correct. In case it was unclear, I didn't mean to imply that I'm "cured", only that I've never had an outbreak since then.

Here is a nice round up of the known evidence: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419779/

TLDR: "Longer duration controlled studies of daily lysine doses exceeding 1.2 g/d are required to definitively test its role in herpes simplex prophylaxis"

EDIT: After reading through the provided table, to me it seems that most studies show little to no evidence that Lysine doses help against the virus. It looks like it's mostly placebo. (Disclaimer, I am not a virologist, this is my take on the paper.)

I used to supplement with a huge oversupply of lysine, enough that I could smell it on my skin, and taste it in my saliva. I could never detect any effect, whether shortening an outbreak, reducing severity, or preventing an outbreak. I have had to conclude that nerve cells that host the virus manage to keep excess lysine outside the cell.

A peanut or nut binge would definitely worsen an outbreak, though.

Oral acyclovir also has no effect on the strain(s) I have. I have had an outbreak start while taking acyclovir prophylactically, and proceed through the whole cycle.

Valacyclovir 1000mg still works. Initially, one tablet. Now, 2 or 3.

Basically yes, but the good news is there’s still plenty of time to find a cure before it hits you.

Maybe. Maybe not. To know that for sure, you'd want two large studies to be done. One showing correlation between having cold sores and AD. And then, one where some people are cured of HSV (I don't think we really have a cure yet...) and where others are given a placebo, with long term tracking to see if intervention reduces AD. That sort of work is how the link between cholesterol levels and heart failures was demonstrated.

This paper isn't even really about the Alzheimers-herpes link, it's more about demoing how you can use HSV-1 with their brain structure to get what looks like a good model of Alzheimers disease. What they gave the model might not even be "real" Alzheimers. Their goal was to develop a really good research tool[0], not necessarily to show an AD/HSV link, and the cells in their model, as induced neuronal stem cells redifferentiated into brain-like tissue on a scaffold, might not be truly reacting like cells in your brain.

[0] from the discussion in the paper, here's the first line emphasizing the takeaway:

"Generating in vitro human models of sporadic AD poses a considerable challenge because of the complex, undefined etiology and slow disease progression that naturally occurs in patients. Here, we describe a multidisciplinary approach to address this critical need by generating robust and physiologically relevant 3D human tissues for studying sporadic AD through the use of hiNSC technology and HSV-1 in combination with a bioengineered brain tissue model."

The herpes-AD link is somewhat supported by this since clearly adding HSV to this brain model caused these AD-like developments, but that could be a factor of how the cells used to make these models react and their physiology might be different as differentiated induced stem cells.

I am very curious to see where this research goes. At the risk of sounding like an absolute nut-case, I've been experiencing significant cognitive decline since getting divorced and becoming sexually active. Granted, I went through a traumatic experience(divorce), developed sleep apnea(treated for ~2 years), and am in my mid-40s, so my concerns are probably unfounded. That said, I've had my apnea under control for some time, I've gotten fit, and tried every combination of supplements I can think of. My hormones and blood work all look fine. Maybe I'll try some valacyclovir and see what happens.

Make sure you get 8 hours of sleep each night. Eat healthy. Exercise daily. Keep anxiety in check.

Yep. I had insomnia for a while but that seems to be in check now. I started intermittent fasting a few weeks ago. No big changes yet, but I'll see how it goes. I also started 750mg of NMN. I've been going back to my old supplement regimen since it seemed to work better for me(moderate dose of vitamins, ashwagandha, CDP choline, high-DHA fish oil, NAC). I tried eliminating a lot of them for several months but it just seemed to accelerate the decline.

How have you been measuring your cognitive decline?

I have much shifted priorities from when I was in my 20s and was never that smart to begin with, so I’m note sure how I would even start to measure it.

I wish I had an objective test. All I can go by is the difficulty I experience solving problems and my progress at work. There are certain classes of problems, boolean logic for instance, which used to be second nature to me but now leave me feeling blank and without even a hint of what the answer is. It even shows up in everyday life. I encounter more and more situations where I can't take the available information and generate a solid decision... I end up 'YOLO'ing it a lot and just taking a guess. I'm trying to come up with coping strategies, like writing things down and using visual tricks, but it doesn't work most of the time. It's frustrating and scary. I don't even know if I could transition from a tech role into management because I am so unfocused and unable to think.

It depends on how you define the cognitive decline. If it’s losing your creativity, generating less ideas, not being able to be focused on a book - it may be a psychological trauma. I would recommend going to a good psychologist and trying to see if something is behind your current state.

Hard to find a good psychiatrist in this town. I just blew $300 on a guy that was obsessed with explaining the details of Passover to me. I had to keep bringing him back to discussing my history and he didn't seem overly interested in it.

I'm pretty sure I have some mix of OCD, mild type-II bipolar, and ADHD. It never seemed to get in my way throughout my 20s and 30s, but lately things have gone downhill.

I have a similar experience except younger but the antiviral doesn't seem to do much for cognitive decline IME. I'm waiting to get jaw surgery in the hope of ditching CPAP.

I do not like headlines that say 'scientists show link between x and y'. It sounds too causal. Rather, journalists should try to write 'scientists observed x correlates with y'

They didn't observe a correlation, though. They observed Herpes causing Alzheimers lesions in vitro.

It should be very easy to test for correlation though since both conditions are usually medically documented. If the correlation is not that high then this story probably doesn’t mean all that much.

This is my primary concern with SARSCoV2. Seeing how HPV can manifest in cancer, how HSV-1 can lead to Alzheimer’s, or how VZV (chickenpox) can flare up later in life as Shingles.

Edit: thanks for the helpful information below!

So far, the coronaviruses don't seem to establish latency in the same way that HPV does. And the chickenpox virus, VZV, is actually also a herpesvirus, along with the Epstein Barr virus and CMV (you might know them as mono), and all those viruses share the characteristics of having latent forms that persist and can re-emerge. While we need to keep our eyes open with SARS-COV-2, especially on cases of potential re-emergence of the virus, it doesn't currently have the type of biology that would make latent infections/these sorts of outcomes a major concern.

Indeed, the long-term effects I've seen researchers express more concern over are simpler. The disease causes quite a lot of damage to the lungs and circulatory system, and messes with brain oxygen levels. Not all of that damage is easily repaired by the body.

Little I've gleaned, HPV is a DNA virus. Those can easily become latent. Where coronaviruses are RNA viruses which don't appear too. A couple of conronavirurs cause mild colds they don't appear to stick around. So you would assume SARS-COV2 to behave the same way.

Also the flu is a segmented RNA virus. The RNA is composed of segments. Which allows it to mutate by shuffling those segments with other strains. Including zoonotic strains. Coronaviruses have a single RNA strand and so don't shuffle.

It's not necessarily an rna vs dna thing. HIV is an rna virus and notoriously goes latent.

You are right in that HIV is an RNA virus and achieves latency, but it doesn't attain latency in its RNA form, but from the RNA being converted to DNA and then incorporated into the host cell's chromosomal DNA (in DNA form). It then sticks around for the duration of the cell's life and any of its descendants. That's why HIV is called a retrovirus, because it creates DNA from RNA during its life cycle.

RNA is chemically less stable than DNA so the latter is more suited for viruses with long genomes as well as viruses which want to go latent. Not an expert. Would be curious if there are viruses that are latent while being in RNA form.

Anyways, Coronaviruses are no retroviruses and their entire lifecycle is in RNA form, so there is no danger of them becoming latent from what I could gather.

Hep C in its chronic form isn't exactly "latent" in the way that a lentivirus or a herpesvirus can be, but it's the closest thing I can think of in terms of an RNA virus that replicates with RNA dependent RNA polymerase that has something resembling a "latent" form. It still replicates and has turnover due to the low stability of RNA as you mentioned, but it stays asymptomatic for decades in this infection course. I"m sure a virologist might be able to chime in with a better example, maybe a nonhuman one? There's so much variation in biology it'd almost be surprising if some RNA virus somewhere hadn't figured out some weird way to stabilize an RNA episome somehow

https://en.wikipedia.org/wiki/Hepatitis_C#Chronic_infection https://en.wikipedia.org/wiki/Hepatitis_C_virus#Replication

Sort of tangential but interesting article in Economist [0] (based on [1]) that links the increased mortality of 28-year-olds of the Spanish flu with the Russian flu 28 years earlier, i.e. when they were born.

[0] https://www.economist.com/science-and-technology/2020/04/25/...

[1] https://www.ncbi.nlm.nih.gov/pubmed/23940526

At this point, is there anything not linked to Alzheimer’s? Herpes does make sense as a plausible factor, but I feel like I read “X linked to Alzheimer’s” every few months.

I worked with a guy researching the functional basis of Alzheimer's synthesizing many radiological technologies.

It is likely a multi-factor pathological degenerative condition with many, many potential precipitating (no pun intended) causes, both nature and nurture.

"The cure" is more than likely a holistic combination of many early lifestyle modifications including, but not limited to: diet, sleep, exercise, gene therapy, immunotherapy, medications, and supplements.

That has been said about every illness that has subsequently been shown to have a single cause.

Long-form article in NYTimes in July of last year.

https://www.nytimes.com/2019/07/02/magazine/dead-pig-brains-...

Thank you for sharing this! We are working on the genomics of AD

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