Beyond headlines of transmitted Alzheimer's, scientists see case for prions(fiercebiotech.com)
fiercebiotech.com
Beyond headlines of transmitted Alzheimer's, scientists see case for prions
https://www.fiercebiotech.com/research/alzheimers-transmission-medical-procedure-builds-case-prion-theory
44 comments
I'm sorry that you're going through this.
I know this is a shot in the dark, I posted this the other day. There's a correlation between poor oral hygiene and dementia/Alzheimer's.
https://www.health.harvard.edu/mind-and-mood/good-oral-healt...
My dad had an infection in his teeth and died with cognitive decline.
The infection isn't always visible, even with a standard X-ray from the dentist.
You'll want to get a "cone CT scan". Not every dentistry will have this equipment. But it's your best bet for finding a festering, chronic dental inflammation.
I know this is a shot in the dark, I posted this the other day. There's a correlation between poor oral hygiene and dementia/Alzheimer's.
https://www.health.harvard.edu/mind-and-mood/good-oral-healt...
My dad had an infection in his teeth and died with cognitive decline.
The infection isn't always visible, even with a standard X-ray from the dentist.
You'll want to get a "cone CT scan". Not every dentistry will have this equipment. But it's your best bet for finding a festering, chronic dental inflammation.
Brush and floss religiously, folks. Tooth bacteria can migrate and be implicated in all sorts of shit: heart disease, colon cancer, dementia.
It’s also very likely there are sins microbiomes that are more stubborn than others, where this advice isn’t effective
We need more effective easily accessible solutions
We need more effective easily accessible solutions
Give zerocarb, particularly high fat zerocarb a chance. Ketones heal the brain. Metabolic theory of dementia too. It's still making its way up to the mainstream but it'll eventually get there.
But you need to be aware that low carb high fat diet does come with slower thinking. It's temporary but you will be tempted to ditch it to "keep up" with outside demand
Are you willing to share more about how you detected/measured the decline?
I have felt a bit paranoid it's happening to me but I'm not sure how to be sure.
I have felt a bit paranoid it's happening to me but I'm not sure how to be sure.
Sorry to respond late, not sure if you will see this. My primary concerns are the fact that I hallucinate (animals, people, objects), get lost/confused in my own neighborhood, and memory issues (can't recall family member names, word finding issues, and can't keep count to 10 when I'm exercising for example). Now this is tricky because I've also had schizotypal personality disorder and ADHD since my teens, but never any visual hallucinations or memory problems until recently. My hallucinations are not the scary type either. For example I'll hallucinate seeing a large cat run down my hallway and I'll step out of the way for it, except I don't have any pets. A 4x4 post can briefly turn into a person. Lastly I was given a brief cognitive test in my doctor's office and I scored at the same level as someone with dementia.
It's important to emphasize this may not be dementia, and could be something else entirely like hormones, liver, thyroid, or other neurological problems that mimic the symptoms of dementia/alzheimers. That being said, dementia is what my doctor has sent me to a neurologist for and what we're testing for.
It's important to emphasize this may not be dementia, and could be something else entirely like hormones, liver, thyroid, or other neurological problems that mimic the symptoms of dementia/alzheimers. That being said, dementia is what my doctor has sent me to a neurologist for and what we're testing for.
Gotcha, yeah those are much more overt than I was expecting. I hope you get it figured out. I was expecting it would be more like generic concentration and memory issues.
For what it's worth, my dad got a form of dementia and the hallucinations weren't part of it. It was more just forgetting things that he had always known, like the road network around where I grew up. My mom said he would call sometimes and say he couldn't remember how to get home from places where he had been many times. Also just a change in affect overall which wasn't obvious at the time, because of how gradual it happened, but later was very obvious in retrospect.
For what it's worth, my dad got a form of dementia and the hallucinations weren't part of it. It was more just forgetting things that he had always known, like the road network around where I grew up. My mom said he would call sometimes and say he couldn't remember how to get home from places where he had been many times. Also just a change in affect overall which wasn't obvious at the time, because of how gradual it happened, but later was very obvious in retrospect.
The headline is wrong. The case is not for prions, but for prion-like behaviour in amyloid beta plaques. They found that this could have been a cause of transmission in rare cases where people received hGH sourced from contaminated cadavers and 5 out of 1800 developed early onset Alzheimer's. But they also had 200+ other people develop Creutzfeldt-Jakob, which is actually known to be caused by prions. So there might be some similarity that enables transmission in a related way. Or there might just be related symptoms. Either way, it is completely irrelevant for normal people, unless you eat squirrel brains or ground up beef imported from Britain in the 90s.
Unless I missed something, it’s weaker than that. What’s the evidence that the contaminant that transmitted Alzheimer’s was amyloid beta or even a related substance?
The hGH was inadequately purified. It seems likely to have contained multiple different contaminants.
The hGH was inadequately purified. It seems likely to have contained multiple different contaminants.
That's why I explicitly said could in italics. Because not even that is certain.
> But they also had 200+ other people develop Creutzfeldt-Jakob
Goodness! 200 out of 1800 subjects developing CJD is the scariest thing I saw in that study. It isn't many folds away from being an extinction level threat. Makes me worry about exponentially rising compute capability.
> Either way, it is completely irrelevant for normal people, unless you eat squirrel brains or ground up beef imported from Britain in the 90s.
Most cases of CJD we see are sporadic CJD. It's rare, but also the scariest struggle I've ever seen.
Goodness! 200 out of 1800 subjects developing CJD is the scariest thing I saw in that study. It isn't many folds away from being an extinction level threat. Makes me worry about exponentially rising compute capability.
> Either way, it is completely irrelevant for normal people, unless you eat squirrel brains or ground up beef imported from Britain in the 90s.
Most cases of CJD we see are sporadic CJD. It's rare, but also the scariest struggle I've ever seen.
Prions are concerning. We know very little about them and have no cures. There are forms for common animals that we eat, like cows. Our processing of these animals leads to 100s or 1000s of unique DNA being identified in a single package of ground beef. They do not test for BSE unless the cows are symptomatic, but it's unlikely they would be symptomatic when they have a typical market time of only 18 months. BSE is thought to be a potential cause of CFJ in humans.
In my opinion, our industrialization of the food supply will lead to mass prion distribution/infection at some point.
In my opinion, our industrialization of the food supply will lead to mass prion distribution/infection at some point.
Prions are indeed very concerning on a concrete per-instance basis, but —unlike viruses— not that concerning in the abstract as a generic threat. Prions as a phenomenon do not exploit an essential feature of our metabolism, and cannot 'evolve' per se, but are limited to the specific cases in which a) a given protein sequence can stably misfold rendering it ineffective, b) exposure of already functionally 'eufolded' proteins to the misfolded one can trigger subsequent misfolding, and c) misfolded versions of the protein can and do consistently come in contact with non-misfolded functional ones.
I'm not trying to downplay the threat and incredible difficulty of preventing known prion diseases, particularly with regards to destroying the infectious prions. However, to illustrate the rarity of the phenomenon on a per-protein basis, consider how the processes involved in cooking have themselves been denaturing (i.e. mifolding) an unimaginable number of all kinds of proteins in a myriad of ways all since human prehistory, and yet we have no known examples nor even hints of new prions having been created in the process.
I'm not trying to downplay the threat and incredible difficulty of preventing known prion diseases, particularly with regards to destroying the infectious prions. However, to illustrate the rarity of the phenomenon on a per-protein basis, consider how the processes involved in cooking have themselves been denaturing (i.e. mifolding) an unimaginable number of all kinds of proteins in a myriad of ways all since human prehistory, and yet we have no known examples nor even hints of new prions having been created in the process.
The mass processing of food could be the additional mechanism allowing mass distribution of prions, no?
Through processed foods, an apex predator like humanity comes into contact with proteins from several orders magnitude more animals than our ancient hunter gatherers or farmers. This problem is compounded as our livestock eat processed foods themselves.
Perhaps prions were not as dangerous for most of evolutionary history as they simply lacked a distribution vector?
Through processed foods, an apex predator like humanity comes into contact with proteins from several orders magnitude more animals than our ancient hunter gatherers or farmers. This problem is compounded as our livestock eat processed foods themselves.
Perhaps prions were not as dangerous for most of evolutionary history as they simply lacked a distribution vector?
> The mass processing of food could be the additional mechanism allowing mass distribution of prions, no?
My grandmother was from "the old country" and would never allow us to buy ground meat in a package. She made us ask the deli to grind her selected cuts, in front of her.
Back then, I wrote this off as some kind of old world silliness. I remember being embarrassed about the whole kerfuffle.
I know she wasn't thinking of prions, just contamination in general.
Now I realize that I was the silly one, and she was very wise.
My grandmother was from "the old country" and would never allow us to buy ground meat in a package. She made us ask the deli to grind her selected cuts, in front of her.
Back then, I wrote this off as some kind of old world silliness. I remember being embarrassed about the whole kerfuffle.
I know she wasn't thinking of prions, just contamination in general.
Now I realize that I was the silly one, and she was very wise.
Probably more about getting known cut/fresh meat. Easier to see what you're buying before it's ground.
Also they don't can't sterilize the grinder between customers so doubt it does much for hygiene.
This is very common around here.
Also they don't can't sterilize the grinder between customers so doubt it does much for hygiene.
This is very common around here.
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I was in grad school with a bunch of people from other countries (a common situation, obviously). Almost to a person, they were deeply suspicious of ground meat.
If the feed restrictions don't work, we don't have any checks in place. With stuff like CAFOs and an 18 month time to market, it's possible we create conditions that can spread prions quickly buy they get to slaughter before they become symptomatic. We won't know until it's already a massive issue.
It already has with the BSE crisis, and I'm not sure if we 100% understand how close to a much greater crises we came. I remember there was period in the UK back in the nineties where there was the grim prospect of hundreds of thousands of cases - thankfully it never came close to that. And there are European countries where I still can't donate blood, because I lived in the UK during the outbreak.
"I'm not sure if we 100% understand how close to a much greater crises we came."
That's basically my point. It doesn't seem like we changed our practices that much. I would have thought we'd test the animals, process them separately, etc.
That's basically my point. It doesn't seem like we changed our practices that much. I would have thought we'd test the animals, process them separately, etc.
There were lots of changes that permeated far beyond Britain. There was a time when every cow was tested in Germany if it was merely alive during the time when contaminated animal-based feed was going around, even if it wasn't fed anything like that. The EU only lifted general testing like 10 years ago - 20 years after the original outbreak. People have also completely stopped using the kind of feed ingredients that allow transmission of the disease to livestock intended for human consumption in most parts of the world. It was a shitty situation, especially in Britain, and many people there probably still carry the disease without knowing it because it can take up to 50 years to show symptoms. That's also the reason why many countries still won't allow you to donate blood if you lived in Britain at the time as the other comment mentioned. So saying that we didn't learn from it or changed nothing is just wrong. Another outbreak like the original one is basically impossible in the western world.
My understanding is that one of the changes we made is we stopped feeding cow brains to other cows, which was the root cause of the problem.
There's also the non-typical BSE - or BSE that is spontaneous. Typically this only affects older cattle.
The interesting thing is that for other prions like scapie and CWD are thought to spread through body fluids and feces and be available in the environment for years. But I don't see any of these concerns listed with BSE. Makes me wonder how much is guess work and how much is confirmed about any of them. But I suspect environmental contamination could be a possible vector. If spread through stuff like urine and feces, CAFOs could be a significant source. This could be a problem if they can be infected for years before symptoms arise, while time to market is 18 months.
The interesting thing is that for other prions like scapie and CWD are thought to spread through body fluids and feces and be available in the environment for years. But I don't see any of these concerns listed with BSE. Makes me wonder how much is guess work and how much is confirmed about any of them. But I suspect environmental contamination could be a possible vector. If spread through stuff like urine and feces, CAFOs could be a significant source. This could be a problem if they can be infected for years before symptoms arise, while time to market is 18 months.
My personal pet theory was that prions are an evolutionary mechanism which prevents cannibalism in mammals.
I know nothing about evolutionary biology, and I wonder if there is any chance that this is true.
I know nothing about evolutionary biology, and I wonder if there is any chance that this is true.
I think your theory makes a lot of sense if you reverse the causality: Mammals have evolved to not engage in cannibalism to avoid prions. Other diseases as well, of course.
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One of the first thing you learn in evolutionary biology is that evolution doesn’t have intent.
Yeah, I guess even I know better than that and should have chosen my words more carefully.
Also not a biologist, but as I understand it: Every living creature synthesizes proteins. Every time you synthesize a protein, there is a tiny tiny chance that it synthesizes "backward". Backward proteins are physically incompatible with "forward" proteins, and also increase the risk that more proteins synthesize backward. It leads to a cascade of errors where lots of proteins synthesize backward and the cells and internal structures can no longer function. It's like you fall apart due to half your Lego bricks being upside-down. And, this is all a statistical probability that could occur in any moment to any living organism.
The evolutionary defenses are to break apart all incoming proteins and reassemble them yourself, and have a cycle of life that starts new organisms from scratch. Large carnivores can't hope to break apart every incoming protein, though. So, basically our lifespans and reproduction method of growing up from a single cell are the evolutionary defenses against the natural phenomenon of prions. But yes, prion disease is probably what forces all higher foodchain animals to avoid cannibalism.
The evolutionary defenses are to break apart all incoming proteins and reassemble them yourself, and have a cycle of life that starts new organisms from scratch. Large carnivores can't hope to break apart every incoming protein, though. So, basically our lifespans and reproduction method of growing up from a single cell are the evolutionary defenses against the natural phenomenon of prions. But yes, prion disease is probably what forces all higher foodchain animals to avoid cannibalism.
This is not at all how it works. Prion diseases are not at all to do with synthesising proteins 'backwards'. It's entirely because of one protein found in the brain which has a very stable misfolded form which will induce other copies of it to misfold as well (and this misfolds all stick together into something the body struggles to break down, which is what eventually causes the damage). It's not something that can happen to just any protein (lots of other proteins do misfold or are otherwise not made correctly, all the time. But they don't induce other proteins to misfold and the body can easily break them down or otherwise get rid of them)
(in fact, the misfolded form is so stable it can survive cooking, autoclaving(!), sitting in soil for years, and digestion. The main reason it's not a big threat is that it needs to somehow get from the environment into the brain, generally via the gut, which is not a particularly easy process for an inert clump of amino acids: a significant percentage of UK residents actually have detectable levels of this prion in their gut already, but only a very small fraction will develop the disease)
(in fact, the misfolded form is so stable it can survive cooking, autoclaving(!), sitting in soil for years, and digestion. The main reason it's not a big threat is that it needs to somehow get from the environment into the brain, generally via the gut, which is not a particularly easy process for an inert clump of amino acids: a significant percentage of UK residents actually have detectable levels of this prion in their gut already, but only a very small fraction will develop the disease)
So that has raised an interesting question in my mind. But as far as I know the only significant case of prion disease amongst human beings, excluding CJD which seems to be generically determined, was the instance of Kuru among the Papau New Guinea tribes; however we know other societies practiced cannibalism at a certain scale such as the Aztecs in which people were eating other people all over the place, yet we don't have widespread evidence of Kuru.
Is there something distinct about Brian tissue which puts it at a higher risk for prion disease formation?
Is there something distinct about Brian tissue which puts it at a higher risk for prion disease formation?
Just a bystander shooting from the hip, but does the fact that brain nerve cells aren't recycled and rebuilt but live as long as the person does mean they are more prone to accumulating bad proteins?
Other tissue like skin or muscle that regularly break down and regrow would offer a lot more opportunity for the body to filter out the prions, but once in the brain cells, there's nothing for them to do but accumulate.
Other tissue like skin or muscle that regularly break down and regrow would offer a lot more opportunity for the body to filter out the prions, but once in the brain cells, there's nothing for them to do but accumulate.
It's because the prion protein is in the brain. As in, there is basically only one protein in mammals which actually has this problem (that we know of), it's not a general issue with proteins. The variants which exist are essentially because of the small variations in this protein across species, or specific inheritable mutations which make sponteneous formation of the misfolded form more likely.
(this protein, by the way, is not essential for life, but lacking it seems to slow brain development in mice)
(this protein, by the way, is not essential for life, but lacking it seems to slow brain development in mice)
‘Prevents’ is an odd way of putting it.
A thing eating dead instances of its same family is already a near ideal situation for passing disease, no fancy evolutionary mechanism required. Frankly, hard to imagine a better one.
If mammals needed a ‘anti cannibalism’ evolutionary mechanism there are plenty of other mechanisms - like disgust responses - that would actually prevent disease.
A thing eating dead instances of its same family is already a near ideal situation for passing disease, no fancy evolutionary mechanism required. Frankly, hard to imagine a better one.
If mammals needed a ‘anti cannibalism’ evolutionary mechanism there are plenty of other mechanisms - like disgust responses - that would actually prevent disease.
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It’s interesting how popular Alzheimer’s research is on HN. I don’t really see any other website talk about it. I have multiple grandparents who were destroyed by it. I guess it is a scary future to look to
I appreciate that HN follows the research, and have wondered if others have had the same experience as me. My mother was diagnosed with Early-Onset Alzheimer's at age 57 in 2013. The progression was slow at first, but it was a major problem for our family by 2017, and she died at 65 in 2022. My dad died of health issues seriously exacerbated by grief of what had happened. It destroyed my family. I'm still in my 30s and both of my parents are gone. This all happened during what are supposed to be the most critical years of a person's tech career. I am almost done with handling my parent's affairs, and am preparing to make major changes to my life again.
Alzheimer's is a terrible disease that is going to wreck havoc on the lives of of countless millenials/genzs as their baby boomer parent's age into it. We need to understand this disease as soon as possible.
Alzheimer's is a terrible disease that is going to wreck havoc on the lives of of countless millenials/genzs as their baby boomer parent's age into it. We need to understand this disease as soon as possible.
That could be the most annoying mobile site I can remember. The number of popups and re-layouts is ridiculous.
I'm currently under investigation of early-onset dementia due to significant cognitive decline in the last year or so with the earliest of symptoms being noticed about 6 years ago. This topic is particularly interesting because I had a cervical spine fusion 6 years ago with a cadaver bone used from an elderly patient. That was the beginning of my journey in hell. It seems extremely unlikely that was a route for transmitting anything to me, but nevertheless the topic posed in this article and the underlying reference articles makes me wonder. If anything, I'm grateful that it's being looked at more closely.