
Using human brain tissue in lab, researchers show herpes link to Alzheimer’s - vo2maxer
https://www.statnews.com/2020/05/06/researchers-show-herpes-link-to-alzheimers/
======
vikramkr
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](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.sciencedirect.com/science/article/pii/S2213671116301412)

[https://www.nature.com/articles/nprot.2015.091](https://www.nature.com/articles/nprot.2015.091)

~~~
Natsu
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)

~~~
guiambros
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._

------
weiming
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](https://www.cdc.gov/std/herpes/stdfact-herpes-detailed.htm))

~~~
echelon
> 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](https://www.cdc.gov/nchs/products/databriefs/db304.htm)

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

~~~
serf
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.

~~~
bryanrasmussen
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.

------
toomuchtodo
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...](https://www.nccc-online.org/hpvcervical-cancer/cervical-cancer-
overview/)

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

~~~
seesawtron
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.

~~~
toomuchtodo
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.

~~~
TaylorAlexander
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.

~~~
toomuchtodo
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.

~~~
TaylorAlexander
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!

~~~
toomuchtodo
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...](https://theconversation.com/alzheimers-disease-mounting-evidence-
that-herpes-virus-is-a-cause-104943) (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.

~~~
TaylorAlexander
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.

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

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

~~~
igravious
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](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](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](https://news.ycombinator.com/item?id=17366591)

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

~~~
Swannie
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.

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

------
pharke
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.

~~~
vmception
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.

------
Grazester
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.

~~~
ianai
Quick google does that’s been investigated

~~~
nickff
It looks like there are some ongoing studies:

[https://www.ncbi.nlm.nih.gov/pubmed/32034019](https://www.ncbi.nlm.nih.gov/pubmed/32034019)

[https://www.nia.nih.gov/alzheimers/clinical-
trials/valacyclo...](https://www.nia.nih.gov/alzheimers/clinical-
trials/valacyclovir-mild-alzheimers-disease)

------
_prototype_
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...](https://www.who.int/en/news-room/fact-
sheets/detail/herpes-simplex-virus)

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

~~~
vikramkr
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...](https://www.nia.nih.gov/health/what-causes-alzheimers-disease#risk)

"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.

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

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

------
01100011
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.

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

~~~
01100011
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.

~~~
ohyes
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.

~~~
01100011
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.

------
clircle
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'

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

~~~
trianglem
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.

------
nostromo
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!

~~~
vikramkr
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.

~~~
Gibbon1
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.

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

~~~
est31
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.

~~~
vikramkr
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#Chronic_infection)
[https://en.wikipedia.org/wiki/Hepatitis_C_virus#Replication](https://en.wikipedia.org/wiki/Hepatitis_C_virus#Replication)

------
ashtonkem
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.

------
paypalcust83
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.

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

------
just42
Long-form article in NYTimes in July of last year.

[https://www.nytimes.com/2019/07/02/magazine/dead-pig-
brains-...](https://www.nytimes.com/2019/07/02/magazine/dead-pig-brains-
reanimation.html)

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

