
The Case for Transmissible Alzheimer's Grows - pseudolus
https://blogs.scientificamerican.com/artful-amoeba/the-case-for-transmissible-alzheimers-grows/
======
nonbel
An increase in amyloids will be observed any time cells are malfunctioning for
whatever reason.

They are the most thermodynamically stable structure that polypeptides can
form, and require constant housekeeping to prevent. Accumulation of amyloids
is like failing to taking out the trash in your house.

Afaik, there has never been a disease state checked for amyloids that failed
to be associated with them (heart disease, cancer, stroke, etc).

> _" From a wide range of in vitro experiments on peptides and proteins we now
> know that the formation of amyloid structures is not a rare phenomenon
> associated with a small number of diseases but rather that it reflects a
> well-defined structural form of the protein that is an alternative to the
> native state — a form that may in principle be adopted by many, if not all,
> polypeptide sequences

[...]

These observations, therefore, have led to the remarkable conclusion that, at
the concentrations present in living systems, the native states may not always
represent the absolute free energy minima of the corresponding polypeptide
chains — the native form of a protein could in some cases simply be a
metastable monomeric (or functionally oligomeric) state that is separated from
its polymeric amyloid form by high kinetic barriers"_
[http://www.ncbi.nlm.nih.gov/pubmed/24854788](http://www.ncbi.nlm.nih.gov/pubmed/24854788)

I've previously commented the same thing:

[https://news.ycombinator.com/item?id=14914528#14917057](https://news.ycombinator.com/item?id=14914528#14917057)

[https://hn.algolia.com/?query=amyloid%20nonbel&sort=byPopula...](https://hn.algolia.com/?query=amyloid%20nonbel&sort=byPopularity&prefix&page=0&dateRange=all&type=comment)

~~~
TheSoftwareGuy
That's fascinating! I wonder if we could ever get to a point where people
regularly can check their amyloid levels to see if they are becoming ill

~~~
nonbel
Not a bad idea in principle.

In practice you have to figure out a way to detect them non-destructively (eg
via light interacting with it in the tissue or some metabolite in excretions).

------
SideburnsOfDoom
Does this line of inquiry mesh at all with the idea that "Gum disease–causing
bacteria could spur Alzheimer’s"

Or are they competing hypotheses?

reported here in January:
[https://news.ycombinator.com/item?id=18987015](https://news.ycombinator.com/item?id=18987015)

~~~
manmal
My wife‘s grandmother had all her teeth pulled and replaced with implants
(probably a hint towards lifelong gum issues, and PERHAPS stirring/aggravating
infections), and 2 years later developed aggressive Alzheimer’s, dying about 3
years later. She was only 64 when she died. To my knowledge, she never had any
neuro or eye surgery. It’s just n=1 of course, but to me the gum disease
hypothesis looks way more promising.

~~~
SubiculumCode
Or perhaps infection by prions by metal dental equipment.

~~~
manmal
Unlikely because only eye and neuro tissue would carry prions for
contamination of equipment, right? Dental equipment should never come in
contact with such tissue.

~~~
b_tterc_p
Aren’t gums chock full of nervous tissues?

~~~
manmal
Oh yes, you are right. I hope this whole issue will trigger some research.
With these massive costs for Alzheimer's treatment coming towards them, even
insurances should be interested in real advancements by now.

------
bitexploder
Just a clarifying point from the article: Transmissible != Communicable.
Still, it makes me wonder what sort of other spooky “life forms” we can host.

~~~
iambateman
(1) thanks for clarifying, that's a relief. (2) what _does_ transmissible
mean, then?

~~~
mikeash
As far as I can tell, the two words mean the same thing. The other commenter
may have meant to contrast with “contagious,” which means that it’s not just
possible but reasonably easy to transmit the disease. From the article:

“It is important – imperative – to emphasize that transmissible does not equal
contagious. There is absolutely no evidence that people with dementia can
spread their disease casually to people around them. Even donated blood
appears to be safe, as no association with blood transfusions and Alzheimer’s
Disease has ever been detected.”

------
colanderman
Dumb question (Wikipedia was of no help), if amyloid beta looks and acts like
a prion, why isn't it classified as a prion?

~~~
subroutine
There is a huge misconception about what is meant by the word "prion". Get
this... there is only one (1) prion protein! All mammalian prion diseases are
directly related to the PRNP gene. People talk about Mad Cow, Kuru,
Creutzfeldt-Jacobs, Chronic Wasting Disease, Scrapie, and a dozen other
diseases like they are not all manifestations of the same underlying problem
with PRNP gene variants. People talk about "prions" as a general category of
proteins capable of causing chain reaction misfolding... which is indeed what
happens with PRNP variants, but not a whole bunch of different proteins --
just those transcribed from PRNP (the prion protein gene). We will probably
discover that other proteins do this to some extent, but it'd still be weird
to call it "a prion" because it's not a proten encoded by the prion gene. Does
that make sense?

~~~
nonbel
You don't share any links, but how would you reconcile this with the claims
that amyloids are widespread. I posted about it here:
[https://news.ycombinator.com/item?id=19129157](https://news.ycombinator.com/item?id=19129157)

Is it really the case that PRNP
([https://en.wikipedia.org/wiki/PRNP](https://en.wikipedia.org/wiki/PRNP)) is
the only known amyloid to be infectious?

~~~
subroutine
My comment wasn't so much on the biology, or whether other proteins could
display 'prion- _like_ ' behavior; it was more so to clarify what I think is a
misuse/misunderstanding of the word 'prion'. I say this as someone who
perpetuated this misuse until a few months ago, after reading an article about
'prions' in the retina, and spent half the day trying to figure out what the
prion protein was, only to discover there was a gene that encoded PRioN
Protein (PRNP); that is, we have a specific protein called 'prion protein'
PrP. So to ask whether something is a prion suggests a misconception, since
that's like asking "is insulin a keratin?" or "is melanopsin an actin?", and
the answer would be, _of course not_ , since those are all names of different
proteins. Now, asking whether some protein X has properties similar to PrP is
a totally legit question (i.e. "is X prion-like?" = great question; "is X a
prion" = probably a misconception).

~~~
nonbel
Thanks. It is also not clear to me after a quick search whether any amyloid
has been called "infectious" other than ones derived from the PRNP sequence.
It is very interesting.

~~~
subroutine
I'm telling you-- i went down the prion rabbit hole myself recently and the
entire path is littered with misconception and inconsistencies in how the term
"prion" is being used.

One place to start other than wikipedia is this cdc site that lists know prion
diseases...

[https://www.cdc.gov/prions/index.html](https://www.cdc.gov/prions/index.html)

After some digging, I concluded that all the diseases they listed are related
to PRNP. Please, please, correct me if I'm wrong.

I'm actually going to chat with a friend in a few minutes who is a postdoc at
MIT studying protein (mis)folding, and said he could help clarify. (i'll relay
any new insights...)

~~~
subroutine
Follow-up -- Spoke with my postdoc friend who informed me there are basically
3 definitions of prion being used in the literature (outside formal reports,
he contends that, just as 'epigenetics' evolved to mean nothing in particular,
the term 'prion' could mean almost anything). The big three:

1\. The purists say prions are _protein-only infectious agent_ ; and they have
a strong case since the word prion was coined as an abbreviation for
"proteinaceous infectious particle". However the specific prion protein
underlying these various diseases were all turning out to be the same thing.

> _This evidence has led to the now widely accepted prion theory, which states
> that the cellular protein PrP is the sole causative agent of prion diseases;
> there is no nucleic acid involved. The theory holds that PrP is normally in
> a stable shape (pN) that does not cause disease. The protein can be flipped,
> however, into an abnormal shape (pD) that does cause disease. pD is
> infectious because it can associate with pN and convert it to pD, in an
> exponential process--each pD can convert more pN to pD._
    
    
      What is a Prion - Scientific America
      https://www.scientificamerican.com/article/what-is-a-prion-specifica/
    
    

2\. So they officially named this protein (drumroll) _prion protein_ (PrP),
and the PrP gene was named PRNP (PRioN Protein). Yep, there is literally a
"prion protein". This protein called prion protein is probably like any other
highly conserved protein, and performs important every-day cell stuff. So
prion protein does not usually display prion-like behavior

Not confused yet? Don't worry, there is a 3rd definition that has taken
shape...

3\. Self-templating. The word "prion" or "prion-like" has come to mean any
protein that display self-templating, and is usually talked about in
conjunction with epigenetic inheritance. My postdoc buddy contends this 3rd
definition is winning the useage war, and so when he hears "prion", he assumes
"proteins that can fold into multiple conformations with some being self-
propagating." A very clear example of this usage can be found in this article
on yeast (and no, it doesn't involve PRNP analogs):
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319070/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319070/)

~~~
nonbel
Interesting, thanks for the history.

------
ipunchghosts
I think it's true that neurosurgeons have a higher rate of Alzheimer's than
the population. This always bothered me.

~~~
sandebert
Source?

~~~
barbarr
[https://thejns.org/abstract/journals/j-neurosurg/113/3/artic...](https://thejns.org/abstract/journals/j-neurosurg/113/3/article-p474.xml)

~~~
nradov
Is it possible that neurosurgeons don't actually have a higher rate of
Alzheimer's Disease, but just get correctly diagnosed more often than the
general population? I suspect a lot of poor people with limited access to
health care die of that disease but it never gets labeled or recorded. But
neurosurgeons can recognize their own symptoms and generally have access to
the best possible care.

The only way to be sure would be to perform detailed autopsies on a large
random sample of the population.

~~~
IAmGraydon
The problem with that theory is that they get diagnosed at a higher rate than
other types of surgeons. This would indicate that their direct exposure to
something related to the neuro part of their job title is involved.

------
abecode
I went to a talk recently [1] in which the researcher explained a theory of
the origin of life where early cell membranes were based on amyloids. The
theory can be described as ocean vent metabolism and amino-acid first (as
opposed to tide pool and radiation/lightning RNA) and it's definitely not the
most accepted theory but it's pretty interesting. Here's an open paper [2] and
the speaker's homepage [3]

[1] [https://www.eventbrite.com/e/ieee-buenaventura-embs-talk-
fig...](https://www.eventbrite.com/e/ieee-buenaventura-embs-talk-figuring-out-
how-life-first-took-off-is-like-rocket-science-tickets-54311847197#)

[2]
[https://biologydirect.biomedcentral.com/articles/10.1186/174...](https://biologydirect.biomedcentral.com/articles/10.1186/1745-6150-3-3)

[3]
[https://science.jpl.nasa.gov/people/Russell/](https://science.jpl.nasa.gov/people/Russell/)

------
autokad
> "In the original Alzheimer’s transmissibility study, scientists examined the
> brains of eight patients treated with prion-contaminated human growth
> hormone as children who decades later died from prion disease (out of over
> 30,000 people so treated, more than 200 died this way). "

does anyone have any clarification on this? to me that is very alarming.
that's about .67% which sounds small, but its int he ball bark of catching HIV
after having unprotected intercourse (depending on a lot of factors)

~~~
pbhjpbhj
How does that compare to control? 200 : 30k sounds like it's lower than normal
"infection" rate?

------
rasengan
One of the less highlighted shocks here is that sterilization is not perfect.

~~~
b_tterc_p
When even bleach doesn’t work, you’re gonna have a bad time.

------
subcosmos
I'm starting to doubt the prion hypothesis now that we know amyloid-beta
encapsulates viral particles in the brain. I think its more likely that viral
infections are the transmitted agent.

~~~
ruytlm
[https://www.statnews.com/2018/10/29/alzheimers-research-
outs...](https://www.statnews.com/2018/10/29/alzheimers-research-outsider-
bucked-prevailing-theory/)

You may find this interesting.

------
b_tterc_p
(In response to comments about eye care tools being contaminated)

What’s preventing someone from testing 20 optometrists’ tools for prions and
settling this?

------
aiyodev
If prions stick to surgical instruments “like glue” what about needles and
lancets? Could this be the link between diabetes and Alzheimer’s?

~~~
intenseparty
Is this thought experiment how antivaxx happens?

~~~
charlieflowers
Careful thought is the _opposite_ of how antivax happens.

------
coffeebean
Would be interesting to find out if increases in the frequency of other
neurologic diseases could be prion-related. Autism, for one.

------
nkingsy
Great. Another reason to regret my lasik.

~~~
mongol
What other reasons do you have?

~~~
nkingsy
Dreading needing reading glasses. Night vision subjectively feels worse.
Random yellow spots in changing light conditions that I don’t remember having
before.

~~~
uncleberg
Forgive me; isn't Lasik all via laser though?

Isn't this more like - you share binoculars with someone and your eye fluids
mix (if you both push them too close)?

~~~
beering
The steps of fixing your eyeballs in place and peeling back the cut-out flap
require physical contact with tools.

~~~
DoingIsLearning
But those are all tools that interface with the anterior cornea part of the
eye.

Is it correct to assume that the type of contact that would be a risk in this
case, is with posterior vitreo retinal surgery where you _might_ have contact
with the optical nerve tissue?

------
acd
What about the Alzehemiers link to HPV virus that formes plaques in the brain?
How is that related to transmitable peptiods?

What is it with the cell membranes size of these viruses that can travel up
and form plaques in the brain?

Alzhemiers hpv link sciencedaily.com/releases/2008/12/081207134109.htm

------
coldcode
The more we study the human body, the more questions we get. I wonder if some
future Dr. McCoy centuries from now will we us as we do medicine of two
centuries ago. We can go to other planets and invent new tech every day, but
the body still holds a ton of mysteries.

~~~
joejerryronnie
Almost certainly. Medical professionals of the future will look at today’s
cutting edge med tech the way we view blood-letting and balancing out the
body’s humours.

~~~
IAmGraydon
Unlikely. Blood letting and balancing out the body’s humors don’t work. At
all. We are quite certain that today’s medical technology works. It could work
better, but we can indeed cure ailments that were once considered incurable.
Medical professionals of the future will look back on today’s medicine the way
we look back on pioneers of science who helped us get where we are today. To
say otherwise is a complete insult of the medical professionals who have
dedicated their lives to developing better medical technology.

~~~
lymeeducator
Blood letting does work for some conditions like "hemochromatosis", in many
cases a result of genetics + iron intake.
[https://en.wikipedia.org/wiki/Iron_overload](https://en.wikipedia.org/wiki/Iron_overload)

------
mhkool
Dr Dale Bredesen has a treatment protocol that _improves_ the conditions of
all patients from moderately (late Alzheimer) to significantly (early
Alzheimer). His treatment protocol recognizes 3 different types/causes of
Alzheimer with an additional 2 subtypes. In December 2018 Dr Bredesen
published an article where he shows the results of treatment of 100 patients
in various health centers: [https://www.omicsonline.org/open-access/reversal-
of-cognitiv...](https://www.omicsonline.org/open-access/reversal-of-cognitive-
decline-100-patients-2161-0460-1000450.pdf) It is a shame that Scientific
American does not know of Dr Bredesen since he is publishing about his
treatment a long time. In 2014 he published an article where he reversed
Alzheimer in 9 out of 10 patients (which are still well in December 2018!).

~~~
jayess
OMICS is one of those fake-journal publication companies. Anyone can publish
anything by paying their fee. The paper's own footnote shows this: Submitted
October 8, 2018; Accepted October 12, 2018; Published October 19, 2018. No
serious journal has a process that quick.

There was a talk at Defcon last year about this. Two journalists from Germany
submitted a jibberish paper to one of these companies, got it published, and
then they went on a "speaking tour," also organized by these fake journal
companies.

[http://www.eevblog.com/forum/chat/journalists-find-fake-
scie...](http://www.eevblog.com/forum/chat/journalists-find-fake-science-news-
agencies-defcon/)

------
analog31
Ask HN: Are there readily available chemicals that will break down proteins,
that would work on prions? How do our digestive systems do it?

~~~
awakeasleep
Anything that you think of as 'corrosive' will generally break down proteins.
Strong bases or acids.

~~~
DaiPlusPlus
Unfortunately they also tend to break down living tissue too.

Relevant XKCD: [https://xkcd.com/1217/](https://xkcd.com/1217/)

~~~
pbhjpbhj
Does a [bullet from a] handgun [effectively] kill cancer cells in a petri
dish? I'd expect it to smash the dish and move the cells but except for areas
with localised heating not to really do anything else?

------
leoh
This makes me wonder if people who wear contact lenses might be at higher risk
as contact lens users regularly touch their eyes.

------
jonahx
Should I actually reconsider having my lasik touched up?

------
discordianfish
So better skip eye exams?

~~~
moreati
What eye exam(s) involve physical contact between the eyeball and a medical
instrument? Or did a joke just go sailing over my head?

~~~
ckucera
Checking eye pressure involves an instrument touching the eye, and is pretty
routine.

~~~
rbobby
My guy uses a machine that does a puff of air. I've never had my eyeball
physically touched by anything at an ophthalmologists office.

~~~
lurquer
Lucky you. I've had injections into my eyeball every few years due to a retina
issue. Imagine a metal clip holding your eyelid open, and watching the tip of
a hypodermic needle approaching your eyeball, held by an older ophthalmologist
with shaky hands.

~~~
acct1771
You don't ask your friends if that's normal, and never go back to that eye
doctor?

~~~
lurquer
Funny you mention that... He was the fourth ophthalmologist I went to
complaining of difficulty seeing. The first three recommended reading glasses.

He, the fourth, was the only one that had me look at an Amsler Grid whereupon,
for the first time, I realized my vision in one eye was completely warped.
Turned out I had a big blister, more or less, behind my retina.

So, is he old with shaky hands? Yes. But, better an old shaky-handed doctor
who knows what the hell he's doing than a young steady-handed doctor who knows
nothing.

Pars Planitis is what it's called by the way. A shot of steroid into the back
of the eyeball and the swelling -- and distorted visions -- disappears for 6
to 18 months. (You don't want to know how you get a needle into the BACK of
the eyeball.... suffice to say, the shaky-handed doctor grabs your eyeball,
rotates the shit out of it until you are staring into your own brain, and then
jabs you with the needle... all the while saying comforting things like,
"Don't move or you might go blind.")

