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
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.
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.
well, Alzheimer's has been highly correlated with diabetes (which diabetes is correlated with gum disease), so its hard to tell. If I were to guess, given if there is a correlation with gum disease and Alzheimer's, I would bet my money that what ever causes gum disease also causes at least some Alzheimer's - not that being treated for gum disease causes it.
My concern is that having general high amounts of inflammation in your body alone increases your risk for Alzheimer's. As someone with inflammation diseases galore (including gum disease), I hope I'm just making inferences where there's no data to support them. Anyone know if that's the case?
1. If certain Prion disease(like say CJD) was Communicable with a high R0 by say contact, fecal matter, saliva we would see a lot of people dying, since CJD has a mortality rate of 90% within 1 year.
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. CJD is only one specific instance of Prion disease. Others (e.g. vCJD) have incubation periods of - multiple decades -. From the article: "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"
Alzheimers is growing at epidemic proportions, globally .
Alzheimers in the US is growing at alarming rates .
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 
 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.
 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?
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.”
Could be wrong but communicable means you can infect other people around you. Transmissible means the disease does generalize to some extent and is caused by something replicable. That is, if they take some of the prions infecting you and inject it into someone else, it can infect someone else. Broken arms and bad genes aren’t transmissible. Lots of cancers aren’t either (meaning I can’t inject you with my cancer and infect you)
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.
Not the same terms per se, but if you are one there is a massively greater chance that you might be the other too. This is an area where we should perhaps be wary.
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.
Amyloid-Beta is a specific instance of amyloids, while prions are a class of amyloids:
>"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.
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?
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).
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
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/
You seem to be mixing terms a bit, so at risk of repeating things you know, I will explain what I am reading from what you've linked.
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.
>"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.
I can't give you a source like that. From the Wikipedia article on prions, it appears that several prion-based diseases are suspected, but that so far the only proven cause for such a disease has been the "major prion protein." In 2015 a hypothesis was advanced that multiple system atrophy (Shy–Drager syndrome) was caused by a prion form of the alpha-synuclein molecule. However, if any subsequent proof has followed, neither the wikipedia pages on prions or alpha-synuclein have caught up with that.
It does seem like Abeta and prions should be in the same class.
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 .
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?
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.
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.
A possible explanation could be based on research suggesting that regular lack of deep sleep increases risk of Alzheimer’s. Given that Neurosurgeons have a grueling 7-8? year residency period after medical school, it would be possible that they undersleep far more than the control group.
I would like to see how the prevalence of Alzheimer's among Neurosurgeons compares against a population with similar work/sleep schedules (eg. finance)
From cursory googling it looks common for programs to expect you to work right up to the legal limit (80 hours/week based on 4-week averages) during residency. Having 16 hour days for ~7-8 years means that you probably have to get used to being a bit sleep deprived all the time.
Part of the problem apart from handover (which wouldn't typically affect surgeons), is the level of complexity. Much of the idea of the modern surgical training (and many other fields) is that the only way of learning well enough is to do, as much as possible. So we push surgeons to carry out as many surgeries as humanly possible.
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).
Yes, I've read this several times: it's the handover that is most problematic.
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.
I went to a talk recently  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  and the speaker's homepage 
> "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)
Would be interesting to see the rate of Alzheimer's among addicts and former addicts. But I imagine the sets "IV drug users who share needles" and "people who live to be old enough to be at risk for dementia" don't really intersect in any meaningful way.
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.
I think we often forget that each generation always thinks they are at the peak of technology except for what they are yet to discover or solve. That is of course completely tautological, but there is a point hidden in there! For instance people in a pre-germ era were not in constant reflection on the inadequacy of e.g. miasma theory. Instead miasma theory was taken as an assumption and so things it failed to explain were not attributed to its inefficiency, but as to other things that had yet to be explained or discovered.
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?
> 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?
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.
Not so certainly. Climate change could ravage the world hard and natural resources could dwindle to almost nothing, putting the race in a crude survivalist mindset where there is no time to improve modern medicine or even learn it. Generations of the future may just as likely be looking back at our tech today in awe.
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...
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!).
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.
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?
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.
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.")
I remember having that done one too, so I looked into it more. There are two types of "tonometry machines", non-contact and contact. The contact tonometers indent your cornea to make measurements (after your eye has been given anesthetic drops). The non-contact "air puff" machines are more common, but apparently not as accurate.
So people who are inclined to avoid direct instrument-to-eye contact can request the "air puff" method.