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

I've previously commented the same thing:

https://news.ycombinator.com/item?id=14914528#14917057

https://hn.algolia.com/?query=amyloid%20nonbel&sort=byPopula...

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).

If you have any examples of these "uninformed scientists" on display it may be helpful to others. The purpose is not to point fingers, but to see where things may have gone wrong.

Just like sneezing/coughing does occur normally, but is also a symptom of many different health issues, and in the worst cases could lead to broken ribs, etc.

Or are they competing hypotheses?

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

Age when teeth are pulled probably correlates well with age when Alzheimer's is first noticed.

It's like "newspapers cause cigarette addiction, people always buy cigarettes in stores where they sell newspapers" [apparent correlation; insufficient observation].

There was another HN thread about the "indestructibility" of prions, and I believe there is a growing consensus that they are not removed by existing techniques within dentistry.

If #2 then I'd venture to say that in many / most cases that correlates with abuse of sweets (read: sugar) which would all effect the teeth (and perhaps in turn the gums).

It's unlikely that simple. That said , I'd venture to say aggregate increase in sugar consumption correlates to increases in Alzheimer's. Yes, as do plenty of other mod cons.

2. The level of A-beta protein(i.e. not technically prion just yet) again the deposits in 7 of the 8 patients was so severe that if this were communicable easily with a high R0, it would also be seen in the general population by now.

So one does not need to worry at least about communicability of this through those means just yet. But transmission if postulated experimentally through certain means like say dental health can mean that we might be able to put a dent in a health crisis of a greying population.

[1] https://en.wikipedia.org/wiki/Basic_reproduction_number [2]https://en.wikipedia.org/wiki/Creutzfeldt%E2%80%93Jakob_dise...

Alzheimers is growing at epidemic proportions, globally [1].

Alzheimers in the US is growing at alarming rates [2].

[1] https://www.alzheimers.net/alzheimers-is-on-the-rise-in-thes...

[2] https://www.alz.org/alzheimers-dementia/facts-figures

  Alzheimers in the US is growing at alarming rates

What I want to know is whether the probability of developing the disease given I am a X year old healthy male/female has increased.

It also doesn’t mean it’s not communicable or contagious, it means we don’t know because it seems no one have looked yet [1]

[0] 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.

[1] Since Alzheimer’s Disease is so common, and we have not (to my knowledge) been looking for Alzheimer's caused by surgical or other medical procedures that access eye or neural tissue -- particularly in patients for whom the appearance of Alzheimer’s would not be surprising -- is it possible that we are underestimating the transmission potential of this disease, and that such events are less rare than we would guess?

“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.”

This isn’t especially surprising. It’s about on par with Alzheimer’s being caused by a microorganism. If we accept that this is true, then it follows that Alzheimer’s, as a symptom, can be transmitted. But unless there is a noteworthy vector of transmission, there’s nothing to worry about.

Speculation about eye care equipment sounds like sensationalism until tested.

If evidence of transmission between people comes forward, the sociological implications will mean decades of debate. Im not going to fault anyone for taking a keen interest in this area. They are opening a pandora's box.

That's a good point for those who just skip straight to the comments, but you should edit this to use the language of the article (contagious vs communicable)

>"Some amyloid proteins are infectious; these are called prions in which the infectious form can act as a template to convert other non-infectious proteins into infectious form." https://en.wikipedia.org/wiki/Amyloid

So if amyloid-beta is determined to be "infectious" (however that is done) then it would be put in the prion subclass of amyloids.

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

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

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...)

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/

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/

PRNP is the gene encoding for "the major prion protein." Several different errors in PRNP create versions of "the major prion protein" that can be folded in a way that is bad (the prion folding). However, that is not the only way in which the proteins can fold themselves.

When lots of these proteins stuck together in an 'amyloid' (starch-like) aggregation, a misfolded (bad) shape of the protein serves as a template, folding more and more instances of the protein into the bad shape.

We consider the shape to be 'bad' because it is associated with visible symptoms of disease.

It is the prion ('bad') folding of a protein which would be infectious.

There are lots of different proteins that create amyloids, but so far all symptoms of prion-type disease for which a cause has been found have turned out to be associated with errors in PRNP.

Thanks, this is an interesting new fact to me if true. Is there a source for it?

I don't mean a source proving there are no others or something else silly like that. I mean like a review article that mentions they couldn't find any publication about any amyloid beyond PRNP-derived ones being transmitted.

A possible practical reason to keep them separated would be to avoid having various safety committees at X research institution from adding dozens of barriers to already difficult Alzheimer's research. Doing work with prions is a little like doing B. anthracis (Anthrax) research in some places - having to deal with indestructible spores.

Not that those safety measures shouldn't be put in place, but it'd make Alzheimer's/Abeta research slower and more expensive. The jump from BSL-1 to BSL2+/BSL-3 is huge [0].

[0] https://blink.ucsd.edu/safety/research-lab/biosafety/contain...

What is the difference between amyloid and prions? Are they part of a spectrum? Are they one in the same? If not, what is the difference? Can what we’ve learned about the biology of prions help our efforts to fight amyloid dementias?

That is, I'd expect cases of Alzheimer deaths to be higher in the wealthy just because I'd expect they would live longer and not die of other ailments before Alzheimer's "got them".

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

I would like to see how the prevalence of Alzheimer's among Neurosurgeons compares against a population with similar work/sleep schedules (eg. finance)

Whether we have the balance right in terms of maximizing repetition vs. minimizing mistakes from tiredness is a good question, but it's not a given that reducing the number of hours worked for surgeons would improve patient survival without a great deal of care in how (e.g. ensuring you cut their number of hours without reducing their critical skillset).

The airline industry was forced to stop pushing people so hard, the medical profession should do the same.

However, IMO you can do things to mitigate this but it involves paying workers who aren't working at full capacity; basically doubling staffing costs I think. If you have a large shift handover period, a staff member doesn't take on a new patient unless they can finish their active input within the shift, it goes to the people sitting idle waiting on the next shift - people are never under a single worker for less than a half-shift; so you can't start with one nurse for half-an-hour at handover and then get passed on, you'd start with that nurse and get half-shift + ½hour. At the back end of the shift the nurse -- and other personnel -- would not be taking on new patients who couldn't be signed-off within their shift, meaning they have fewer patients, meaning they can focus more on handover of the patients for whom it's necessary.

There's probably holes in that, it's like reverse pipelining.

You might get enough effect by having a smaller overlap and having workers shadow the worker who is going off-shift but that's not really reducing handovers so much.

[1] https://www.eventbrite.com/e/ieee-buenaventura-embs-talk-fig...

[2] https://biologydirect.biomedcentral.com/articles/10.1186/174...

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

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)

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

You may find this interesting.

Seems BACE2 might be promising.

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

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?

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

So we know everything, except for what we don't know. And we assume that what we don't know is complex, because otherwise we would surely know it. Yet history shows that's often far from the case. It's just that knowing what you don't know is rather difficult, even when the unknown is very simple, simply because you might not even stop to consider such a possibility. People thought the black plague was wrought and spread by evil spirits. They could have easily managed to prove it was being spread by rats, if they were so inclined, but who'd have thought to consider such things at the time?

For a contemporary example we are now discovering that the gut biome is seemingly associated, perhaps causally one way or the other, with all sort of other characteristics of the body and even the mind (as in the autism : gut biome link). We've had the technology to discover this for centuries, but who in the world would think to bother imagining a connection between your gut and anything besides ailments of the stomach?

Well, about that -

https://www.livescience.com/61444-black-death-cause-found-tr...

https://www.pnas.org/content/115/6/1304

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...

Relevant XKCD: https://xkcd.com/1217/

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.")

The shaky hands? When someone had a needle in your eye, that needle can move your eye in even the steadiest of hands.

My favorite was noticing how the needle had a metallic, rainbow pattern.

So people who are inclined to avoid direct instrument-to-eye contact can request the "air puff" method.