Alzheimer’s cases tied to no-longer-used medical procedure | Hacker News Reader

Alzheimer’s cases tied to no-longer-used medical procedure

statnews.com

531 pointsleeny230 comments

Afaict, this is not an entirely new finding. For example, this page (https://www.nature.com/articles/d41586-018-07771-6) references a 2018 article about the issue of Alzheimer's being transmitted (or rather "seeded") through growth hormone extracted from cadavers. Perhaps the new article provides additional evidence or perhaps the other article only suspected a casual link and this one proves that there is one. I haven't read it thoroughly.

What I find interesting and scary is the "seeding" part. The small amount of growth hormone injected to the children cannot itself have caused Alzheimer's. But it must have caused some rewiring of the brain to make it accumulate more plaque which over a period of many decades slowly decreased their brain performance. If this effect is synthesizeable then one can easily imagine many countries using it to develop terrifying biological weapons.

It mentions brain proteins contaminating it, makes me think of prions.

Yeah, these paragraphs from the paper sounds like the amyloid proteins can sometimes look/act like a prion if you squint:

> The far wider relevance of prion mechanisms was first exemplified with the discovery of yeast prions but has also widened considerably with the recognition that the more common human neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases, involve accumulation and spread of assemblies of misfolded host proteins in what is often described as a ‘prion-like’ fashion with experimental transmission of relevant pathology in primates or mouse models. However, the importance for human disease was unclear until the recognition of human transmission of amyloid-beta (Aβ) pathology via iatrogenic routes after prolonged incubation periods, causing iatrogenic cerebral amyloid angiopathy (CAA) and raising the possibility that iatrogenic Alzheimer’s disease may occur at even longer latency.

The thing is (despite popular misconception that prions are common and many proteins that can turn into prions), there is only a specific protein that can be a prion- the PrP protein.

https://en.wikipedia.org/wiki/Major_prion_protein

Demonstrating "some other other protein behaving like a prion" is close to nobel prize territory.

There are quite a lot of diseases where a prion like mechanism is suspected https://en.wikipedia.org/wiki/Prion#In_other_diseases

ie. some protein other than PrP gets misfolded and then acts as a template to cause more misfolding. I've read up a bit on ALS as my sister has it and while it's not fully understood the most likely cause seems misfolding of a proteins called or TDP-43 or SOD1. Eg from a paper:

>recent cultured cell line and animal model studies suggest that the misfolded forms of SOD1 and TDP-43 do self-propagate within neuronal cells and transmit to neighboring cells https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363329/

Wikipedia seems to say there's another one:

>All known mammalian prion diseases were caused by PrP until 2015, when a prion form of alpha-synuclein was hypothesized to cause multiple system atrophy (MSA).[10]

https://en.wikipedia.org/wiki/Prion

Perhaps a first pass research question is:

Do people who undergo spinal, brain, retinal surgery have a higher incidence of Alzheimer when compared with the rest of the population?

Otherwise there is no point in chasing this "some other other protein behaving like a prion" avenue.

>Do people who undergo spinal, brain, retinal surgery have a higher incidence of Alzheimer when compared with the rest of the population?

In that case scarring/inflammation might trigger the Alzheimer's though. The interesting part in this article is that the growth hormone was not injected into brain tissue I assume.

The article mentions that the procedure was banned due to incidence of Creutzfeldt-Jakob disease. That is a prion disease.

They still use pieces of cadaver for other surgeries. E.g. gum and bone transplants done by periodontists. Seems risky to me.

as long as it’s not spine or brain matter it’s probably okay. During the mad cow outbreak (BSE, the bovine equivalent of CJD) in the UK, they banned “beef on the bone” but not all beef.

And CJD came about from farmers using ground and processed cow brains to feed cows. What could possibly go wrong feeding a cow some cow brains!

It is worse than that - it first made the jump to cows when condemned sheep, infected with the similar prion disease 'scrapie', were ground up and fed to cows.

There's a human prion disease, kuru, which was caused by the practice of funerary cannibalism - where family would ritually consume parts of their deceased relatives' bodies.

The moral of the story seems to be, don't eat brains.

Which is rather unfortunate.

I no longer eat meat, but when I was younger I considered the brains as the tastiest part of an animal, when properly prepared and cooked.

It is said that in USA eating organs is not very popular, so it is likely that many have never experienced well cooked brains, to know what they are missing.

There exists a hypothesis that is rather plausible, that breaking bones and eating their content of brains and marrow has played an important role in the evolution of humans, by providing an abundant source of long-chain fatty acids, enabling the unusual mass ratio between the central nervous system and the whole body that characterizes humans.

Brains, cooked contains 210 calories per 140 g serving. This serving contains 15 g of fat, 16 g of protein and 2.1 g of carbohydrate. The latter is 0 g sugar and 0 g of dietary fiber, the rest is complex carbohydrate. Brains, cooked contains 3.3 g of saturated fat and 4304 mg of cholesterol per serving.

If you do not have risk factors for heart disease, you should limit your cholesterol intake to no more than 300 milligrams a day.

1000% your rda of cholesterol in a single serving!

Periodontists have been also linked with a higher number of Alzheimer cases. Is a group of risk in this disease.

The doctor or their patients have the higher risk?

if I remember correctly Dentists had more cases of alzheimer than other groups of doctors. I heard it some time ago.

If is a prion, it should resist most sterilization of dental instruments by heat on autoclave. So is obvious IMAO that this could be a way to spread the disease from one patient to other, but I'm not an expert on clinic procedures and the protocols may have been updated. This is known, or at least suspected, since maybe a decade or so.

>Dentists had more cases of alzheimer than other groups of doctors

Herpes?

1. Travels along nerve cells

2. Causes lifelong infection

3. Can enter the brain (HSV encephalitis)

4. Herpetic whitlow used to be an occupational disease of dental workers (still is to some extent)

"Overwhelming Evidence for a Major Role for Herpes Simplex Virus Type 1 (HSV1) in Alzheimer’s Disease (AD); Underwhelming Evidence against"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234998/

do you recall percentages? like 10% higher or 5x higher?

Don't remember, sorry. It was a lot of time ago. The articles should be listed in scientific indexes.

Dentists are a special group that worked a lot with mercury in the past, dunno if is related but it could be a combination of risk factors. We should ask a chemist.

In any case today the facts can be very different.

Might depend on the age of the patient.

What I found odd, is in the article it talked of the importance of sterilising medical tools used, that may have had prions on them. Prions can't even be destroyed by extreme temperatures, they are extremely scary.

Over 900c for several hours vs 250 in autoclave... if Alzhaimers can spread this way, i am done, because I spent days in dentist chair...

Prions are exactly the tiny, hard to detect things that could make Alzheimers transmissible. There are likely to remain many questions to resolve, but this sure suggests a line of inquiry: Is Alzheimer's one distinct disease? Can a prion be isolated as the cause? Can a diagnostic test be designed that detects this prion? Etc.

Have they found prions in Alzheimers patients universally? That would seem to have come up looooong ago given how much it has been studied.

There is no reason to assume this is a matter of proteins.

It could just as easily be viral or bacterial infection. Classically, people always just assumed that brains had no such infections. Until somebody checked, and they turn out to be very common.

But they still don't look for infections in Alzheimer's patients' brains, probably because it would make them seem negligent. (Which they are.)

> There is no reason to assume this is a matter of proteins.

Except that there's increasing evidence that specific proteins do in fact play a part in various forms of dementia.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072215/

It is possible that Alzheimer's is purely a matter of aberrant proteins. That would be valid conclusion if the evidence turned out to support it. But it is not a valid assumption under any circumstance.

Both new and old articles are from the same lab. So they hypothesized it in previous article and now found signs of dementia in some of patients who survived. Still no evidence of actual transmission of A-Beta.

I wonder what other stuff is being unwittingly transferred during standard blood transfusions. I've seen some interesting research about the "signalling" power of blood from both older and younger donors, with the "young blood" causing a slow down of senescence in cells, and the "old blood" causing a speed-up in senescence. Any time you take biological material out of other human beings and put them in a different body, it seems like you are introducing a lot more uncertainty and risk than when you inject a person with a comparatively "simple" small-molecule drug.

>Any time you take biological material out of other human beings and put them in a different body, it seems like you are introducing a lot more uncertainty and risk

But this always had to be weighed against the risks of not getting the transfusion. Typically the consequences of not getting a transfusion when it is medically indicated is pretty severe.

We don't really need to worry about unlikely not-yet-understood edge cases that happen years later from procedures we've done millions of times. We gotta gotta about blood loss.

Yes, usually if you need a blood transfusion there are bigger issues.

Please remember to ask your doctor about autologous transfusion, where you bank your own blood before a planned procedure.

Depends what the indication is, for some kinds of trauma the evidence is that transfusions are what will keep the patient alive, e.g. you're dumping pints on the table and it's likely to be contaminated, you can't salvage and reinfuse. However, for pre-planned surgery the evidence suggests avoiding blood loss where you can is the best practice. Studies have also shown that pre-deposit autologous blood donation before surgery is of uncertain benefit so it tends to be contra-indicated in the UK at least.

Before we understood the risks we used to do transfusions a lot more frequently than we do now and this led to a generation of anaesthetists who would basically treat with blood transfusion at the slightest sign of low blood count. More recent studies have suggested that a lower blood count can be tolerated than was previously realised and that you can often get away with guaranteed pathogen free (and much cheaper) volume expanders. There has also been developments in cell salvage to reinfuse suctioned blood and methods to avoid blood loss in the first place.

Medical practice has also changed to reflect this and the changed evidence base, especially given the relative costs (hospital managers love to save money). Hip and knee replacement surgery used to use blood routinely and were almost always done under general anaesthetic, but given we now want to get patients out within a day or two post surgery we do the surgery under spinal block and minimise blood loss as much as we can.

tldr; We still need transfusions for some things but we should be using them less than we do.

> I wonder what other stuff is being unwittingly transferred during standard blood transfusions.

Back in the early 1990s my wife worked in epidemiology studies at the national blood agency in our country. There was a lot of work to be done since at the time being a hemophiliac and receiving blood products meant a good chance of dying from AIDS or non-A non-B hepatitis (now known as Hep C). The agency did not test each and every donation for the presence of these pathogens because the available inexpensive tests had a poor success rate (high false positive) and the better tests were prohibitively expensive and the policy was "if we destroyed any suspected donations we'd have to destroy all of them". The idea of a screening questionnaire was floated but because most sexually transmissible diseases are also transmissible through blood, the question "Have you ever had sex?" would eliminate quite a few donations. They were a tough time for the blood agency.

Thankfully technology has progressed and testing for known pathogens in a blood sample is rapid and inexpensive. Testing for unknown pathogens is still a challenge.

Until 2023 male blood donors in Germany were still asked "have you had sex with a man in the last 4 months?" As an exclusion criterium.

Donors who lived in Britain in the 90's are still banned due to the Lack of a Test which can identify 'Mad Cow Disease'.

I thought MCD was relatively fast and aggressive?

If you want to read more about this history in the US, I cannot recommend And the Band Played On highly enough. The book deals with the early history of the HIV/AIDS epidemic and touches on the issues related to blood donations and transfusions given the technical limitations at the time.

It's also a crushingly depressing book.

Yeah, the blood bank companies end up looking really evil in that. If you were a hemophiliac in the early 80s, you were playing Russian roulette constantly.

My mom developed an allergy to eggs after a blood transfusion. She long regretted never being able to eat another chocolate eclair.

That’s nuts. Seems like researchers should look really closely at weird side effects of blood transfusions since these are effectively “natural experiments” that would be impossible or unethical to run normally.

Generally, I think if a patient needs blood transfusions there's a bigger and more immediate life-and-death problem right there. I think allergies would be preferable to death.

Is my understanding correct? I hope blood transfusion hasn't become a routine procedure these days.

I don't think GC was suggesting that we stop blood transfusions, but rather that we do better tracking to improve our understanding in a way that normally would be unethical (if not for the fact that, as you say, blood transfusions are a life-saving intervention).

Yes exactly.

You get a blood transfusion for any major surgery.

Before the 1990's but not anymore. The contaminated blood scandal in the United Kingdom (https://www.infectedbloodinquiry.org.uk/) and a lot of papers showing benefits to avoiding blood loss in the first place have changed practices. We haven't eliminated the use of allogeneic blood transfusions but they're indicated a lot less than they used to be.

Makes me wonder if there is any possibility to give blood in the lead-up to your surgery, such that you're transfused with your own blood?

It's called an autotransfusion and it's a thing.

https://en.wikipedia.org/wiki/Autotransfusion

You get it IF there is a need for it, not always.

I had an open heart surgery and didn't get a blood transfusion.

No.

They do. These incidences are rare, but documented, and researched.

https://www.scientificamerican.com/article/when-peanut-aller...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562830/

It looks like the allergy isn't permanent though.

Well, the boffins figured out somehow that if you get a blood transfusion from an Opossum you become immune to all snake venom for a while.

(Seems wikipedia removed this factoid now... and other sources state "most" snake venom)

I assume they tested on animals, not humans.

Can you provide a source? That sounds unlikely

Here is something scholarly:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5315628/

I cannot find anything now talking about a blood transfusion (I probably read about it 10 years back). It more or less jives with the scholarly article in that "immunogenic effects are reported".

A slightly less dry read:

https://www.grunge.com/1105496/how-an-opossum-could-be-the-r...

No, eggs, not nuts.

I'll see myself out.

As someone who has been deliberately used at a young age by a doctor for a medical experiment, I can tell you this is how human experiments are done these days. Take someone with condition X which is life threatening, and suddenly you can do all your unethical stuff without having to be afraid of consequences. You just have to crank up the severity and you suddenly are free to do whatever you want.

Can you sue?

You are supposed to declare your issues before (or at least after) you give blood. Kinda messed up that whoever donated that blood didn't report it. Then again, I'm glad the blood was available...

We can't conclude that the donor had an egg allergy. The immune system is complicated as hell, it could be the case that he had some weird protein circulating on his blood that was recognized by her immune system, and by chance this protein was structurally close enough to some egg protein that now eggs trigger an immune response on her.

Worth noting that the most prevalent protein in blood is albumin, and the major protein in eggs is, yep, albumin.

Are you implying there is a connection? Even if it's just for nonsense, I'd love to read it. Because other prevalent commonalities, you could make the same argument about water, for example.

"The immune system is complicated as hell."

You got that right! My wife used to eat a banana every day. Then something in her flipped and she reacts as if she is allergic to bananas and the rest of the world - not exaggerating. She can eat a very small number of foods and has to avoid most people because of smells. It isn't allergies it is - you guessed it - her immune system.

If we could just flip it back to "normal"...

Same thing happened to me. I was eating bananas, beef, coffee, etc. then I got some sort of viral infection. My thyroid became inflamed for a couple months. No doctor was able to find anything wrong with me.

Little did I know, having postviral sequelae causes my immune system to start hating many things I used to eat. A food blood sensitive test showed that bananas, beef, coffee were what set my immune system off the most.

I was told it was gut permeability causing food particles to leak into the blood stream causing the immune response. So the fix has been to stop eating those, let the gut heal, and over time I've been able to eat those foods in moderation years later.

Did the smell of a banana, or just having one in the house set you off - or did you have to eat it to have a response?

Only eating bananas

I don't think I ever had to declare allergies when donating my blood (France).

They focus on infections and cancers I think.

Why would they ask for allergies if we don't yet know that they can be transmitted like this?

I thought it was well known that certain allergies (eggs/peanuts) can transfer via transfusions? At least for awhile. It looks like there’s some literature on it at least, but I didn’t dig into it or anything. I just thought this was “common” knowledge since that’s what I was told years ago by a nurse I was dating in college, a long time ago.

I would assume things like that maybe after a bone marrow transplant but having a blood transfusion seems pretty mild I wouldn't expect any affects from it.

Maybe it's known but I don't know about it :-)

Some 30% of people have allergies. It can already be challenging to source enough blood with the current eligible population.

Killjoy note that the allergy may well be unrelated to the transfusion, despite occurring after it.

Though it seems quite plausible something in the blood caused an immune reaction that then also gets set of by egg protein.

FWIW, ChatGPT 3.5 says:

"The development of a new food allergy, such as an allergy to eggs, as a direct result of a blood transfusion is extremely rare and not a well-documented phenomenon. Food allergies are typically triggered by exposure to specific allergenic proteins found in foods, and blood transfusions do not typically involve the introduction of food proteins."

ChatGPT 3.5 is known to make mistakes, hallucinate, and not care about the factuality of its responses.

Given this, a comment which does nothing but quote chatGPT 3.5 verbatim can do more harm than not commenting at all, especially on health matters, where such qualities can constitute outright recklessness.

If you want to share your own thoughts, though, I know I'd welcome them. At least humans have a greater than 0% chance of caring about the well-being of humans.

Dunno but it seems not unheard of see eg. Peanut and fish allergy due to platelet transfusion in a child https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562830/

Eggs or chicken eggs? Could always use duck eggs.

If your mom’s still around let her know about vegan egg alternatives!

I am not a vegan, but I eat a lot of vegetables, most vegetables, if prepared correctly are delicious, there are a lot of traditional dishes in every cuisine in the world that take absolutely no animal products on their preparation and have a wonderful taste and aroma.

I see no reason to eat those franken-foods just because you're a vegan, a lot of them have strange additives to make them taste and look like animal stuff, it is simply not worth the risk to eat them IMHO.

Of course, this is a personal view point.

> I see no reason to eat those franken-foods just because you're a vegan, a lot of them have strange additives to make them taste and look like animal stuff, it is simply not worth the risk to eat them IMHO.

"Just Egg" is mung bean and canola oil. You can DIY it for cheaper, it's like buying pancake mix. There's always a few strange additives for these sorts of products (improve shelf life, anti-caking, emulsion, whatever), but that's not a vegan-specific thing.

Seed oils like canola aren't great for health. They're fairly new to the food stream (only widely available since about 1900), heavily processed, and chock full of compounds the plant was making to protect it's seeds, many of which cause inflammation and other negative health effects. Olive oil, coconut oil, and animal fats have all been in use longer, and seem to be better for us. Avocado oil also seems to be decent, though it can be challenging to find quality unadulterated oils of any kind.

Any proper evidence or is this just some internet meme? https://www.consumerreports.org/health/healthy-eating/do-see...

You're welcome to eat the non-food. I won't stop you.

Aquafaba is a completely natural vegan egg substitute used in baking.

https://en.m.wikipedia.org/wiki/Aquafaba

I’ve used it with amazing success as a non vegan in both chocolate chip cookies and pancakes

She honestly asks me to bring over vegan mayonnaise sometimes. She also has a good egg-free cake recipe.

Vegan egg tastes like butts

> I've seen some interesting research about the "signalling" power of blood from both older and younger donors, with the "young blood" causing a slow down of senescence in cells

Maybe the Silicon Valley ‘blood boy’ can be brought to market.

I believe Ambrosia was the (real) startup that was the inspiration for that story arc.

Looks like they're still around but have pivoted to boring wearables and of course AI.

A supposed win for the FDA, but perhaps a loss to humanity since there does seem to be evidence that the idea actually worked.

For once, a pivot to AI is a bit of a relief...

Not only blood transfusions, but ligament/tendon transplants from cadavers are extremely common for people who tear their ACL.

It would be a disaster if this type of surgery also transmitted some prior/protein misfolding disease decades later. Millions would be impacted. The practice stared in the 1980s, but really only became popular in the early 2000s with the boom in arthroscopic surgery standardization.

Hopefully the blood-brain barrier prevents this.

Oh man, I bet you’re right and enough time hasn’t gone by to see the fallout from it! I bet rich people will start bidding up tendons and ligaments from younger cadavers (probably mostly motorcycle accident victims). Although given that so many of those have toxoplasmosis, maybe that’s also not great…

One estimate says that 30-50% of all human beings have toxoplasmosis, so I would put that as pretty low on the list of risks.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963851/

those tissues are unlikely to carry prions. prions are concentrated in the brain.

Unlikely != zero risk, and concentrated != isolated?

Could they test the donor first for these proteins or whatever is causing it?

We probably could, but only after we'd figure out what exactly is causing it.

> it seems like you are introducing a lot more uncertainty and risk

Of course. What matters though isn't the absolute risk, it's whether such treatments provide enough benefits to outweigh those risks. Not dying outweighs pretty much everything.

> I've seen some interesting research about [...] the "young blood" causing a slow down of senescence in cells,

This is excellent material for the conspiracy theorists.

Yeah see https://techcrunch.com/2017/06/14/no-peter-thiel-is-not-harv...

There is no evidence of actual transfer. It is just a possibile hypothesis.

There is a line of research into the "transmissible' phenomena of a lot of these neurodegen dz. Epidemiologically, it's probably not infectious from one person to another bc we don't see spouses getting PD or AD often. But there's interesting phenomena - i.e. one of the Parkinson's stem cell implantation trials got a lot of press after the trial (which failed, didn't show benefit) bc after subjects passed several years later and got autopsied, they found clumps of parkinsonian proteins (lewy bodies) on the histology slides of the implanted stem cells.

Similarly, there's some papers w/ mice w/ knockout Parkinsonian genes getting parkinsonian features and lewy bodies when injected w/ abnormal misfolded synuclein from another mouse.

What exactly to do w/ this, no one is entirely sure yet.

> we don't see spouses getting PD or AD often

Actually it may seem so [1], though still there is not any conclusive evidence to support a transmission hypothesis really as all this could be due to increased stress and such factors. Also, brain surgeons' increased risk of AD and more reports of associated risks with regard to contamination from brain operations [2] (similar to the article's ones) provide more indications that such a hypothesis is not completely implausible. Though also far from strongly supporting it or anything, as there is no proper experiment design with control groups etc to make better conclusions.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945313/ [2] https://www.medicaldesignandoutsourcing.com/report-suggests-...

Yes there may be these individual case reports - but in practice - I would say, most spouses of PD patients don't seem to get it. There's like 2 exceptions out of 1000 patients in our clinic, but not enough that I feel like running to my epidemiologist with my hair on fire.

I guess if your brain proteins are mixing with someone elses you normally have a bigger issue.

I don't know where your neuro-jack is installed, but if it's not in the skull then I don't know how you even connect to the all-mind.

> What exactly to do w/ this, no one is entirely sure yet.

Sounds like a sensible next step would be to try and replicate this in animal models (i.e. treat animals with growth hormones extracted from cadavers of same species) to identify the proteins/prions that trigger the pathogenesis of Alzheimer's, which could perhaps be drug targets for at least a subset of AD causes.

Can you explain more or give a source on that parkinsons stem cell trial? I’m not sure I understand what happened and I’d like to learn about it.

It's been a while since I looked at this stuff so apologies for the rustiness

Columbia trial paper: https://www.nejm.org/doi/full/10.1056/nejm200103083441002

Tampa trial paper: https://pubmed.ncbi.nlm.nih.gov/12953276/

Additionally, it looks like I totally missed at least one European program at Lund University (review paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345652/)

I've heard rumblings re preclinical prep work w/ the Takashi group at Kyoto University as well, not sure where that's at at the moment.

I randomly found this review, but haven't had a chance to plough thru it yet, but I wouldn't be surprised that the stem cell tech these days makes whatever they used 20 years ago ancient and crude by comparison https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9890289/

Additionally, this was the followup paper that found Lewy bodies developing in the transplanted cells (suggesting some sort of spread/prion-like hypothesis with regards to Lewy bodies/insoluble alpha synuclein)

https://pubmed.ncbi.nlm.nih.gov/18391962/

edit: competing group also managed to publish theirs at the same time

https://pubmed.ncbi.nlm.nih.gov/18391963/

> w/ mice

Is this a special kind of mouse?

w/ = with

w/o = without

This comment is full of abbreviations (PD = Parkinson's Disease, AD = Alzheimer's Disease) that makes it a bit difficult to read (if you don't know / realize what those abbreviations stand for)

Mice are a good animal model for a lot of the human physiology.

"w/" is an abbreviation for "with". "w/ mice" should be read as "with mice".

The savings of just two characters does not worth the effort and mental pause to decode it

It's a great abbreviation for handwriting, though. It also meshes really well with w/o.

not to horrify you but https://gomerblog.com/2014/12/soap-note/

it's an exceptionally common way of writing with and without. similar to "etc." standing for "et cetera." at some point you don't "decode" it, thats just what it means.

the expensive kind...

I thought the beta ameloid theory was largely debunked since the publisher had manipulated data. Now it's attached again? I'm so confused

It's complicated. Read all about it https://www.science.org/content/blog-post/faked-beta-amyloid...

My understanding was the beta-amyloid hypothesis itself is under some amount of scrutiny and may not truly explain Alzheimer's. Wonder if this finding adds more evidence for the amyloid hypothesis.

This finding definitely supports a brain protein hypothesis, but it could just as easily point to tau protein as amyloid.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399531/

The short version as I understand it: amyloid plaques are a symptom but not a cause.

There was a theory floating around that they're a neurological immune response to viral infection but I don't think there's enough evidence to prove that yet.

I thought CJD was caused by a prion. Was it in the growth hormone prep from the cadavers?

From the article:

> In the interim, scientists had discovered that that type of hormone treatment they got could unwittingly transfer bits of protein into recipients’ brains. In some cases, it had induced a fatal brain disease called Creutzfeldt-Jakob disease, or CJD — a finding that led to the banning of the procedure 40 years ago.

Yeah that's correct. The article mentions a few cases of people who died from transmitted CJD that may have also received some beta amyloid or tau proteins that could have catalyzed development into Alzheimer's if only they didn't die from CJD, which seems to develop more quickly through that route. If Alzheimer's is truly is some kind of prion-related disease, which the research is suggesting.

there's transmissible CJD, but most cases are a genetic version where you get the prions from your own cells and then it cascades, if I recall

Not sure why scientists has to pin point a single cause where as you have different vectors that can cause the same disease is also plausible

Or that we've been lumping multiple different types of cognitive decline as a single disease.

Can’t you make a definitive diagnosis from an autopsy. Could be that multiple diseases lead to the same findings in the autopsy.

While someone is alive a diagnosis of Alzheimers is more of a diagnosis of elimination. There are several drugs that can be used to slow the progression and I assume that those have a role to play in solidifying the diagnosis.

You can check for amyloid plaques in an autopsy, but apparently plenty of old people that show no significant cognitive decline also have amyloid plaques.

So, while we would definitively call it Alzheimer's if you have significant cognitive decline + amyloid plaques, it's not 100% clear that this is a single diagnostic.

That ventures wildly into whether the realm of physicalism explains malaises that happen in the "consciousness" realm. spooky

Scientists are a bit more savvy than you are giving them credit. Anything neurological is unlikely to have a silver bullet treatment. So researchers are going after what looks most promising with respect to understanding the disease as well as a path towards treatment. Which is currently AB (or Tau), but there is plenty of skepticism that we are chasing the only measurement we have.

Yet many other correlations are even hazier than AB.

They don't, but my surface understanding is that the medicines that effectively nuke beta amyloid have no effect overall. Which would mean it's not even one of many causes, it seems to not be a cause at all.

I think the medicines likely reduce beta amyloid rather than get rid of all of it which if it has a prion like mechanism wouldn't really fix things.

I don't think scientists are necessarily assuming a single cause so much as that it's a moot point since we still haven't identified any causes for sure.

If some cases are caused by amyloid plaques and some aren't, for example, and we develop a treatment that cures the amyloid plaque cases but not the others, it will probably become extremely obvious that there are different causes at that point.

If they still have some samples of this old, corpse-sourced hormone, perhaps they can analyse them to try isolate candidate compounds.

For CJD the testing isn't needed, it is established that cows eating processed cow brains caused the outbreak.

I've often wondered if Alzheimer's is actually novel instances of prion disease.

For instance, Kuru was developed within I think a handful of generations in a population of ~20,000 with limited opportunities for transmission (only transmitted when someone dies and their family eats their brain).

If the base incidence rate for a novel prion is that high, can you explain Alzheimer's as just that? It would be sad news for pharmaceutical companies - it would render Alzheimer's as a disease in the same class as cancer. Total systems breakdowns that are low-probability but inevitable on a long enough timescale.

it’s almost certainly not, or you would see epidemiological evidence for chains of transmission. prion diseases require contact transmission which is all but absent from the alzheimer’s story.

> it’s almost certainly not, or you would see epidemiological evidence for chains of transmission. prion diseases require contact transmission which is all but absent from the alzheimer’s story.

I think what the parent comment is saying is, what if it isn't transmitted, what if a prion is just occurring in the brains of the people who develop alzheimers?

That seems unlikely to me, but on the other hand, the article seems to be suggesting that transferring brain proteins from people with alzheimers to people who are younger will cause them to develop alzheimers which would be roughly consistent with that.

I don't know whether that would be possible, but, for example, what if there was somehow a specific protein in the brain that could easily be misfolded to become a prion, and the eventually if people live long enough they tend to produce that prion at least once, so it occurs essentially as a result of old age, but it can theoretically also be transmitted in the manner described in the article?

We don't eat the brains of people with Alzheimer's, so we don't see it transmit?

I know CWD transmits from pretty much any shedding of the animal, but is that necessarily universally true?

Can we map that onto human beings who practice hygeine and don't eat leaves that another human urinated on?

consumption of neural tissue isn’t the only transmission vector though. (See TFA for an example, in fact.) If it were a prion disease, just the law of averages dictates that we’d see some transmission from things like organ transplants from pre-symptomatic carriers. There’s no evidence of that at all that i’m aware of. (disclaimer: I work at a startup in cognitive testing, so while i’m certainly not a researcher in the field, i do see quite a bit of research on dementia-adjacent diseases)

But don't you also have a windowing effect there? How many >50 y/o people are donating their organs?

You could also explain the age skewness by allowing for the fact that it takes time for the prions to replicate to the point that you notice symptoms.

Other I think this would predict: lifetime exposure to mutagens is a predictor for Alzheimer's. Alzheimer's is more heritable from the mother than the father.

Is it still possible that the chains are there but are missed because of the disease very slow progress?

4 hours ago: https://news.ycombinator.com/item?id=39179368

Recycled comment follows.

___________

To highlight:

> The authors and other scientists stress that the research is based on a small number of people and is related to medical practices that are no longer used.

Also that there is zero-reason to believe in any person-to-person spread:

> The study does not suggest that forms of dementia such as Alzheimer’s disease can be contagious.

Lastly, a fun vocabulary word [not in that article]: "Iatrogenic" - An illness caused by medical examination or treatment.

Don't forget nosocomial- infections acquired in a healthcare setting.

Another one is "nosocomial" - (disease) originating in a hospital

Alzheimer's as a (transmittable) prion disease is the stuff of nightmares (prion disease == incurable)

This is really fascinating, horrifying and hopeful at the same time.

It makes sense that some neurodegenerative diseases with unknown etiologies are caused by prions or prion-like proteins.

It could be fruitful to study the rate of Alzheimer's among nursing assistants who work in elder care. I found a few resourcas stating a higher rate for caregiver's in general along with nurses.

I have thought decreased immune function from aging leads to the increased permeability of the blood brain barrier: which leads to the infiltration of pathogens and now possibly prions.

I would assume this could be, or possibly has been, studied in animal models.

From my limited understanding the blood brain barrier doesn't really stop things. However it is difficult to transmit from one person / animal to another usually resulting from things like transplants or being injected in.

I just did a brief search and found this article related to the increased permeability of the blood brain barrier with aging.

https://immunityageing.biomedcentral.com/articles/10.1186/s1...

Research into chemical agents that induce or inhibit this would also be of interest.

This is one of the reasons that, despite no direct evidence of harm, I will only ever take marine collagen instead of bovine collagen.

Do not fuck with the possibility of ingesting cow nervous system tissue, let alone human.

Tell that to my heart valve. All bovine baby.

Wild Chronic Wasting Disease + hunting also seems like a bomb waiting to explode sometime.

But, somehow, it hasn’t into humans yet.

why is cow or hunan nervous system tissue particularly dangerous? what animal is marine collagen from and why is it less dangerous?

Prions.

Non-mammal prions have a different enough shape to avoid breaking mammalian biomechanisms.

"Is it circumcision?" I love how this is what people say when reading over my shoulder.

Using herbal natural remedy was what got me tested negative to HSV 2 after being diagnosed for years. I have spent so much funds on medications like acyclovir (Zovirax), Famciclovir (Famvir), and Valacyclovir (Valtrex). But it was all a waste of time and my symptoms got worse. To me It is very bad what Big pharma are doing, why keep making humans suffer greatly just to get profits annually for medications that don't work. I'm glad that herbal remedies are gaining so much awareness and many people are getting off medications and activating their entire body system with natural herbal remedies and they have become holistically healed totally, It’s also crucial to learn as much as you can about your diagnosis. Seek options visit ( worldrehabilitateclinic. com).

So is this small bit of information any use for figuring out the general case?

Yes, definitely. It hints to the root cause being "very similar in many respects to what happens in the human prion diseases like CJD, with the propagation of these abnormal aggregates of misfolded proteins and misshapen proteins."

So while this might be unrelated to the general cases, it's still a promising area of investigation.

Prions are most scary bit of biology there is. Almost impossible to eleminate, causes victim proteins to unfold.

Thanks to CIC Biogune too for the early research:

https://www.cicbiogune.es/news/us-alzheimer-association-fund...

Hmm, I wonder if the same could occur from a bone graft from a cadaver, like for a tooth implant?

I'll admit that I am somewhat ignorant here. But I thoughts the "Alzheimer's is caused by plaque buildup in the brain" theory was on its last leg and pretty much disregarded by most new scientists.

I am also a layman but I believe I’ve read that its no longer believed to be caused by the plaque, but the plaque is a clear signal/comorbidity of the underlying cause - whatever it is?

I'm somewhat surprised by this publication's restraint when referencing Creutzfeldt-Jakob disease, as usually news orgs like mentioning the fact that Creutzfeldt-Jakob is the human form of mad cow disease.

it does say that that BSE is the bovine equivalent of CJD in the article

weird that the bulk of patients are in france and UK, does that indicate diet?

All the researchers are all UK based, and the UK became verrrry interested in prion diseases due to a very bad habit UK agriculture had gotten into of incorporating culled animals (other cattle, which furthered the spread, but the ultimate cause was likely grinding up sheep infected with scrapies, an ovine spongiform encephalopathy) supplementary cattle feed for animals later eaten by humans which led to the CJD outbreak in the UK. European agriculture also had a similar bad habit, but maybe less sheep or scrapies or something?

France probably imported British beef and so were affected also. They certainly banned it the longest afterwards.

And I was about to do the usual Kiwi thing of "Just let the cows eat grass, duh", but every Western country tends to supplementary feed dairy cows, including mine, except we prefer to use palm kernel, thus promoting deforestation in Borneo, yay!

But it turns out a lot of British beef comes from their dairy herds, so "just feed the beef cattle grass" wouldn't have helped.

Cows are also fed “sewage solids” from water treatment plants. Now that I think about it maybe I should stop eating / drinking cow products

Those are hazmat, contaminated with heavy metals among many other things, and need to be disposed of in specific ways - none of which involve consumption.

Cite?

sorry what

do you have a source?

A compelling book on this topic:

https://www.simonandschuster.com/books/Deadly-Feasts/Richard...

My understanding is France has a history of ignoring risks, including intentional spread of HIV to patients:

https://en.wikipedia.org/wiki/Contaminated_blood_scandal_in_...

Interesting since the UK was part of the huge Mad Cow (BSE a variant of Creutzfeldt-Jakob) disaster[1] in Europe back in the 90s which introduced new rules in Switzerland requiring marking origin and banning certain feeding methods.

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

I actually don't believe this conclusion based off the fact that it would be slam-dunk evidence for the pathogenesis of Alzheimer's, which we don't have.

Multiple pathways could lead to the disease.

It's entirely possible that a metabolic dysfunction or viral origin causes immune dysfunction and the downstream dysregulation, misfolding, amyloid/tau signals, etc.

There might be multiple entry points to causing this disease.

That might be true, but I don't think this makes the conclusion any more compelling because it now fails Occam's razor.

Chances are greater the conclusion is simply incorrect.

That's a misapplication of the razor here. The simplest explanation for the statistically unusual prevalence of the disease amongst these patients is indeed that there is a causal link.

Isn't the point that when comparing multiple explanations of a phenomenon one applies Occams razor to pick the "best" one?

In this case we don't have any explanations to compare yet, just suggestive lines of research. So it's premature to bring out the razor.

> it now fails Occam's razor.

I mean, mechanistically speaking, so does cancer. I don't think that's quite the lens to apply to biological systems.

Biology is wildly complex and subverts expectations all the time.

It is the lens to apply to any system.

You don't defend a tenuous conclusion by doubling down with a tenuous defense.

"Science" is constantly inaccurate. I can pull two papers right now with opposing conclusions.

Assuming a scientific conclusion is simply incorrect is a pretty good bet, even if you have absolutely no context or idea what is happening at all.

> It is the lens to apply to any system.

I can point to countless instances where it fails to adequately guide investigation in biology.

Occam's razor leads to premature simplification. When the space is vast, dynamical, and unknown, it's absolutely not a tool.

Do you think, for instance, that V(D)J recombination satisfied Occam's razor when we asked ourselves how adaptive immunity worked, or how some forms of diseases such as SCID manifested?

There is a metric ton of pure serendipity in the study of biology. We're drawing new connections between systems all the time. This is just a new data point.

I think you're misunderstanding slightly the utility function of the logical device here.

It's not so much that we cannot analyze a complex system using this criterion, it's moreso a tool that allows us to identify a logically tenable pathway for investigating a specific element of reality.

For example, a poster above noted that I was misapplying the razor because he went one level below where I was analyzing. He's not necessarily incorrect, and neither am I.

You interrogate reality at multiple levels of magnification, which is why you don't need to know how genes specifically work to know that they work and make predictions based on their prevalence, for example.

New prion diseases are being found in other animals and might evolve to enter humans. There is a deer version being watched - not yet found in people, AFAWK? https://www.cdc.gov/prions/cwd/index.html

There have been many cases of assorted Human Papilloma viruses (HPV) transmitted by kissing as well as assorted variances of oral sex. Recent vaccines are very effective.https://www.cdc.gov/vaccines/vpd/hpv/public/index.html

Do you mean HSV? I have seen articles implicating that virus but it's the first time I've heard of a HPV association.

different to HPV. More on HSV https://www.healthline.com/health/herpes-simplex#causes

What do these two things have to do with each other?

Not much, deer prion wasting disease is forced shape-fold mimicry and HPV is DNA insertions affecting repressed cancer causing genes having increased expression. I referenced it, but it does not really fit in.

Why isn't the procedure used anymore, since they stopped using it before this was discovered?

Second paragraph of the article:

>In the interim, scientists had discovered that that type of hormone treatment they got could unwittingly transfer bits of protein into recipients’ brains. In some cases, it had induced a fatal brain disease called Creutzfeldt-Jakob disease, or CJD — a finding that led to the banning of the procedure 40 years ago.

In other words, it gave people mad cow disease.

Not “mad cow disease”, but CJD.

“Mad Cow Disease” specifically refers to the variant form that is said to have been caused by prions from infected animals turning up in beef products.

Though in fact all we know for sure about the link there is that it’s the same prion in the cattle and human cases; the suggestion that there’s a direct food chain connection is still only considered very likely, not proven.

That's not to mention the zombies. There was a huge cover up.

We worked out to produce these hormones (or equivalent compounds) synthetically, so we no longer need to extract them from the brains of deceased humans, a procedure which risks transmitting disease.

Not just human growth hormone, also other hormones used to be derived this way, e.g. those used to induce ovulation in fertility treatment.

I know someone who received cadaver-derived fertility hormones in the 1980s. She has a small risk of developing CJD and dying from it. It hasn't happened yet, and probably never will, but no one can say for sure if she is infected. If you don't develop symptoms (some people are infected but never progress, others suddenly develop symptoms one day after decades of being asymptomatic), the only way to know for sure if you had it is at autopsy, through destructive testing of brain tissues.

Because it was shown to also spread a prion disease (CJD, though not the variant kind as far as I have understood)

As the article says, there is now a synthetic hormone which is given to the patients. We don't need to extract the hormone from dead people anymore.

Yes, but that just would cause the derived product not to be needed, when it was actually actively banned because it was proven to have caused some cases of CJD.

Did you even try reading? It's made super clear at the start.

Yes, I read the whole thing but I missed the second half of the last sentence of the second paragraph. The fact that one poster replied that it's due to the advent of synthetic hormones and others replied about the spread of CJD indicates it's not super clear, but sibling replies got me the insight I was looking for.

Guys, don't get distracted by all the new mysterious causes of Alzheimers.

Alzheimers is "brain diabetes". You get it from a lifetime of eating carbs and developing insulin resistance.

Big pharma and big agriculture will never want you to know this, so it will take years before this becomes common knowledge.

I wonder what other practices from decades ago are lurking to be discovered as catastrophic to currently living people.

I remember reading about cattle rearing practices a while ago that might be responsible for some prion related diseases. Can’t remember the exact source. These things get you from entirely unrelated sources.

There was a whole epidemic: https://en.wikipedia.org/wiki/United_Kingdom_BSE_outbreak

Give me the friggen files. Here is a hard drive.

I thought it was still early in 2024 and we have this news but good to know you need to actually transplant brain matter to get it

…Michael J. Fox?

This "one weird trick" will eat your brain!

prions

Slightly more clickbaity title than the BBC's "Medicine stopped in 1980s linked to rare Alzheimer's cases"[0] which also says "The findings do not mean Alzheimer's is infectious - you cannot catch it from contact with people who have it... The researchers say all of the people in their study had been treated as a child with cadaver-derived human growth hormone, or c-hGH, that was contaminated with brain proteins that are seen in Alzheimer's disease... used to treat at least 1,848 people in the UK between 1959 and 1985".

[0] https://www.bbc.co.uk/news/health-68126907

I didn't find it clickbaity at all. The contents of the article were exactly what I expected based on the headline, and I didn't know this was possible.

The really interesting thing here is that Alzheimer's seems to be transmissible from person to person via biological material. The BBC headline you quoted, "Medicine stopped in 1980s linked to rare Alzheimer's cases", totally buries the lede and is borderline misleading.

My reading is that m-i-l is using "clickbaity" to mean "doesn't prevent all possible wrong conclusions one could draw from the headline". (In this case, the wrong conclusion would be thinking that because there exists cases of alzheimer being transmitted through some mechanism that Alzheimer was contagious.)

While it's certainly understandable that we are all tired of clickbait that purposefully misleads the reader, imo we should not overcorrect by demanding that headlines cannot be misinterpreted by arbitrarily ignorant readers.

That's right. Living in the UK and taking an interest in popular science during the "mad cow disease crisis"[0], I had been aware that prion diseases can be transmitted in humans if (for example) you eat (infected) brains of your dead ancestors[1], but the headline as originally submitted ("Scientists document first-ever transmitted Alzheimer's cases") did suggest to me that we might be at the start of something altogether new and much more alarming.

[0] https://en.wikipedia.org/wiki/Bovine_spongiform_encephalopat...

[1] https://en.wikipedia.org/wiki/Kuru_(disease)

Ahh, yea, fair. I hadn't realized the headline changed. The original is unnecessarily vague, contributing to misinterpretation without benefit.

I didn't either, and I didn't even read the article. The headline was actually dead on factual for me.

For me as well, and I didn't even read the headline.

>The findings do not mean Alzheimer's is infectious - you cannot catch it from contact with people who have it.

Alzheimer's being an infectious disease is still being researched. The article does nothing to disprove it.

> "The findings do not mean Alzheimer's is infectious"

It may not be infectious like a cold or herpes, but it was amazing to me that it is transmissible. I spent some time Googling and it looks like the appropriate term is "Donor-Derived Infections."

I think that, in principle, any disease that a donor has has some small chance of affecting the recipient. Infections, cancers, prion diseases, toxins are well known to do so, some immune issues also have a clear pathway, but in principle even genetic issues could affect the recipient depending on a whole host of complicated biology that we don't fully understand.

I wonder if we will ever find methods of flushing the brain out or doing anything within the human brain that will allow us to defend against things like this.

I know our brains are very protected in our bodies and for good reason but I still wonder how far we will be able to go if we can ever safely and humanely bypass that.

Reply on news.ycombinator.com