11 ms·
Proteins central to the pathology of Alzheimer’s disease act as prions – study
- amyloid_tau 8y agoPretty awesome work. Looks like we don’t have obvious ways to avoid these classes of proteins in the same way we can just avoid tainted meat and abstain from cannibalism... https://en.wikipedia.org/wiki/Amyloid https://en.wikipedia.org/wiki/Amyloid https://en.wikipedia.org/wiki/Tau_protein https://en.wikipedia.org/wiki/Tau_protein
- bboygravity 8y agoOr do we? People taking acyclovir regularly (to suppress HSV1 and 2 symptoms) have been found to have a 10 fold decrease in risk of getting Alzheimer's (Taiwanese study). https://www.medicalnewstoday.com/articles/322463.php https://www.medicalnewstoday.com/articles/322463.php Additional studies are currently ongoing to confirm this in the US. The scientific "journalists" seem to jump to the conclusion that therefor HSV1,2 must be cuasal for Alzheimer's. But it could be that Acyclovir somehow prevents or slows the formation of AB tau prion-like forms (and has nothing to do with the herpes - Alzheimer's causality). Or. Some Acyclovir prevents Alzheimer's through a completely different mechanism we don't know about yet. My point: effective medication may already be there. We just don't know how it works yet.
- Cosi1125 8y agoOr, you know, it might be that Alzheimer's has an autoimmune factor contributing to it... :-)
- bboygravity 8y agoCan you elaborate? As far as I know the immunesystem "has no access" to the brain? Also by "factor" do you mean protein? I'm just an electronics guy, would love to know more.
- Cosi1125 8y agoSure! It'a common misconception that the brain is completely separated from the immune system. If it were, it would take one evolutionarily successful pathogen to threaten the existence of our species. The brain is indeed (usually) impenetrable to immune cells circulating in the blood stream, but there are "resident" immune cells protecting it from everything that manages to pass all the other barriers. You can read more about it on Wikipedia [1]. By "factor" I didn't mean a biological entity, but rather... well, a factor contributing to the development of the disease. (As you might have noticed, English is not my native tongue, and I couldn't come up with a sophisticated synonym to "a thing that makes a contribution to sth" ;-)) It's been long postulated that AB/tau proteins are only a symptom of Alzheimer's and not a causative agent (which would explain why, so far, no treatment has been successful despite pre-clinical successes). According to some hypotheses, what we observe is the effect of "strayed" lymphocytes going postal and attacking brain cells after being activated by a microbial agent – and HSV is one of the suspects. Hope that helps. If something is not clear, feel free to ask and I'll try to explain :-) [1] https://en.m.wikipedia.org/wiki/Neuroinflammation https://en.m.wikipedia.org/wiki/Neuroinflammation
- dreamcompiler 8y agoThis is an absolutely astonishing game-changer for Alzheimer's research. The scientist who discovered prions (and got a Nobel prize for it) now has convincing evidence that the proteins that cause Alzheimer's are themselves prions. Amazing, scary, and hopeful all at the same time.
- bentona 8y agoTo someone with minimal background in biology, prions are a fascinating and terrifying phenomenon right out of speculative fiction. Absolutely amazing and scary.
- thanatropism 8y agoWell, when you’re an authority on prions everything looks like a prion disease.
- labster 8y agoAs a web developer, I'm curious if Alzheimer's is really a cross-site scripting attack. If so, we could prevent it by encoding the amino entities, and that would be a game changer.
- JoeSamoa 8y agoThe encoding would have to be part of our DNA though right? Do you think this method would work as a treatment or just as a method of prevention? I like your mindset and I think your metaphor may be correct.
- viraptor 8y agoAre there any curable prion diseases right now? As far as I can tell from googling, CJD does not have any known cure. If there aren't, does it mean we need to come up with a completely new class of treatments?
- wpasc 8y agoThere are no current treatments for Alzheimers that do much of anything. If the problem/cause is more confidently known, at least there is a more narrow target to aim at.
- NickM 8y agoThere are no current treatments for Alzheimers that do much of anything. Well, unless you count physical exercise.
- telchar 8y agoSpeculatively, in the future we may be able to design proteins that would target the prions and destroy them or refold them into less harmful shapes. To do that we would need to 1. know what protein shape would be required and 2. be able to figure out how to make that shape (what sequence would happen to fold itself into that shape). I would think we would need to advance quite a bit more in protein science before that is feasible.
- echelon 8y agoJust to provide background, what you describe is nowhere close to feasible. Designing novel proteins is computationally intractable. It took evolution billions of years and parallel optimization to figure out how to problem solve with polypeptides. We're not even at the punch card phase.
- m_mueller 8y agoWould quantum computers with more logical qbits help? My layman impression was that this could solve protein folding.
- josephagoss 8y agoDoes this mean that inflammation of the brain is to be ruled out as a cause?
- cheesymuffin 8y agoWhat is inflammation?
- echelon 8y agoThe immune system kicking into gear. - vasodilation - production of cytokines and chemokines - cell recruitment - cell proliferation - upregulation of certain genes You're kicking your immune system into gear in some shape or form. Keep in mind the immune system is one of the most complex signalling systems in the body. You can trigger it in different ways and get different responses.
- sjg007 8y agoNo..
- thaumasiotes 8y agocheesymuffin's comment is downvoted, but I think he's on to something. It would be very odd to consider inflammation of the brain to be a cause of any problem, because inflammation is a symptom of something else.
- josephagoss 8y agoYeah I agree, however I'd imagine if inflammation was the cause of issues (and I recall some studies showing brain inflammation to be linked to some brain disorders) then perhaps more research would go into what causes the inflammation. Some evidence the inflammation might be diet related too. Although I can't recall the source at the moment.
- Dylan16807 8y agoBeing a symptom doesn't absolve it of being a cause too. If a thousand things can cause inflammation, but then there's a package of symptoms caused by inflammation itself, then it could be worth it to directly fight the inflammation in a lot of cases.
- pretendscholar 8y agoCan someone with a better background tell me if this is a game changer? I thought the consensus was that Alzheimer's probably had a few potential causes.
- icegreentea2 8y agoThere's nothing in principle that prevents other mechanisms from inducing the prion conditions that eventually leads to Alzheimer's symptoms. This paper is just another piece of evidence that points to the plaques and tangles being self propagating, instead of being say for example a pure by-product of some other mechanism. In itself, that doesn't really tell us anything about the mechanisms at play. Is it a game changer? Probably not. It's unlikely that Alzheimer's is purely spread through inter-human prion transmission, so other factors are likely still at play.
- jmpman 8y agoHow does this mesh with the gingivitis correlation?
- BurningFrog 8y agoI wondered the same. I suppose there is nothing saying that it can't be both be a prion disease, and enter the brain through a gingivitis path.
- robbiep 8y agoThere is an inflammatory correlation as well, it may be simply that. I have been out of the AD literature for about 6 years but back in Med school read every major paper from the 80s onwards. The flip flop between tau and AB as the causative agent was very interesting
- deleted 8y ago[deleted]
- cjbprime 8y agoY'all, please never post university press releases about single scientific studies. They are the worst thing. Every major human problem has been declared solved by one of them. They are even worse than posting single scientific study papers themselves at the time of publication, and that's still pretty bad, because of the overwhelming incentive to create exciting studies that are wrong, and our current inability to notice the same due to limitations of peer review in catching results that were created by some form of chance. This result looks very exciting and if it replicates and is built upon in five years' time then we can all talk about it then, you know? I note that Science Translational Medicine's impact factor is not awesome. But even that doesn't mean much to me: lately it feels like _Science_ and _Nature_ are in fact especially likely to collect results that are very exciting and also wrong, because they feel like they're the best journals so their results should be surprising.
- thaumasiotes 8y ago> lately it feels like _Science_ and _Nature_ are in fact especially likely to collect results that are very exciting and also wrong, because they feel like they're the best journals so their results should be surprising. I believe this is accurate on all counts. Slate Star Codex put the issue fairly pithily: there's only one way to get surprising-if-true results that isn't surprising.
- steve19 8y agoCan you explain the joke?
- outlace 8y agoThe only way to get a surprising-if-true result that is not surprising is if the result is not true. Hence the joke is that most of these surprising findings are probably B.S.
- dekhn 8y agoHere's how I explain it: Science and Nature play a role different from other journals. Their role is to stimulate new thoughts amongst the most skilled in the field. Any really good scientist in a field can read a paper published by another really good scientist and hone away the bullshit, but be inspired by the ideas. People who are not skilled in the art of reading a competitive paper are going to be disappointed by the sloppy lab work, sloppy writing, sloppy thinking, because it appears that the overall benefit of disseminating new ideas widely for experts to cogitate on may exceed the value from having "perfectly correct" papers. Case in point: the original DNA structure paper (W&C, 1953) actually had a wrong detailed structure for the DNA (but the right conclusion about how the structure provided a hypothesis for a templating mechanism) because the alcohol concentration used to form the crystal was too high. The value of getting the paper out the community ASAP greatly exceeded the small details that were wrong (which eventually got resolved), because it stimulated the thought of the community around the templating mechanism.
- breck 8y agoA good primer on prions: http://www.prionalliance.org/2013/11/26/what-are-prions/ http://www.prionalliance.org/2013/11/26/what-are-prions/
- jeffdavis 8y agoHow does a protein come to be misfolded? Is it a random mutation that happens to be self-propagating? Is it different between alzheimers and other ones like mad cow?
- purpleidea 8y agoThis is all preliminary, so nobody knows for sure about Alzheimers, but assuming it was, then it would likely be a different protein. (IOW a different linear chain of amino acids, that folded in a non-standard way.)
- jrumbut 8y agoI have no idea what the mechanisms affecting protein folding are in this context, but if you are interested in learning more about how proteins fold and perhaps helping researchers fold interesting new ones, check out FoldIt (a protein folding citizen science project): https://fold.it/portal/ https://fold.it/portal/ It was featured in Werner Herzog's Lo and Behold and I had the privilege of taking a class taught by a professor involved in its development. The community there can do a little bit to restore your faith in humanity and technology.
- hoseja 8y agoThis still exists? I'll have to check it out again sometime...
- robbiep 8y agoThermodynamics. Certain proteins have a propensity to Misfold, this is driven by the folding conformations as well as by Heat Shock Proteins. The underlying genetics that drive amino acid sequence are the basis for this. In the best known prion disease, Mad Cow, one misfolded protein drives other similar proteins it runs into to induce the same conformation. Due to the thermodynamics of folding, it is now in a very stable structure and won’t revert to its original or desired biological structure, is difficult or impossible to clear, and will cause other proteins to fold in the same way.
- 8y ago
- outlace 8y agoThe actual study is here: "Aβ and tau prion-like activities decline with longevity in the Alzheimer’s disease human brain" < https://stm.sciencemag.org/content/11/490/eaat8462 https://stm.sciencemag.org/content/11/490/eaat8462 >
- outlace 8y agoTaken out of context, the press release makes this finding look a lot more ground-breaking than it is after I quickly read through the actual study. Still a good piece of work though. It was already known, as pointed out in the actual paper, that Amyloid-beta (AB) and Tau, the proteins that have long been implicated in Alzheimer's disease (AD), have prion-like properties which means they exist in an abnormal 3D configuration that causes other AB/tau proteins they interact with to adopt this abnormal configuration. But they can also polymerize into large neurofibrillary tangles (NFTs). Patients who died late, e.g. at age 80 with AD had a lot of these NFTs, so it seemed reasonable by many to assume that these NFTs are the major cause of brain deterioration. But there were a number of alternative hypotheses of what exactly AB and tau were doing in the disease. This study suggests that AB and tau cause disease primarily through their prion-like activity and not due to their ability to accumulate into large trash-balls (NFTs). They noted that patients who died young of AD had very few NFTs but have a lot of the AB/tau prion-like forms, whereas patients who survived longer had a lot of NFTs but not a lot of prion activity. This lends evidence to the idea that the primary pathogenicity of AB/tau is through their prion activity and not the fact that they accumulate into large protein blobs.
- autokad 8y agocould that be interpreted as the ones with trash balls (NFTs) might actually be the ones handling it 'better'?
- outlace 8y agoYou mean like the NFTs are somehow protective against the Prion forms? That is a possible interpretation that this study does not directly disambiguate.
- krilly 8y agoCould just be an innocuous buildup with no effects either way, that just results from having the disease a long time. I doubt it's a direct result of handling the disease well but I don't know anything about what defenses our brains have against prions
- 8y ago
- Jasmine_Hubbard 8y agoThis makes the disease even worse than expected and it's already a wicked disease. Has a prion disease ever been treated?
- hansflying 8y agoBad news! Prions are extremely stable and not even boiling, Protease or high radiation can disrupt them.
- londons_explore 8y agoSome prions are extremely stable
- Haga 8y agoThe problem is too little capitalism in science. Hear me out on this one please. We humans have a natural fear of breaking up into small groups and parallel execute counterrunning endavours.
- i_feel_great 8y agoI still remember undergraduate biology class where the lecturer mentioned that crazy idea of proteins being infectious. Most scientist thought the results were errors and that Prusiner was a fool. Even after kuru was proven to be cause by infectious proteins.
- netwanderer3 8y agoIs it possible that these prions were also acquired by human through meat consumption? As in the case with PrP prion from Mad Cow Disease which spread through meat eating as well. Another very similar case is by eating fruit bats containing toxic BMAA, which has a very similar structure to L-Serine amino acid causing it to be picked up instead during the protein synthesis process and resulting in a misfolded version. Studies are being done as BMAA could be a likely cause for many neurological disorders such as Parkinson's. Has there ever been any researches in determining the rates of Alzheimer disease in meat eaters vs. vegetarians?
- stareatgoats 8y agoInteresting topic. Here is an anecdote that I found through a simple web search that somewhat addresses your question: "Few studies have looked carefully at the risk of dementia in vegetarians versus other people, and the data is contradictory. One small study of California residents found that meat eaters were more likely to become demented than their vegetarian counterparts. Another study in Alzheimer’s patients, however, found that adhering to a strict vegetarian diet resulted in lower cognition compared to a pescatarian diet (i.e., a diet that includes fish)." https://www.alzdiscovery.org/cognitive-vitality/blog/vegetarian-and-vegan-diets-for-brain-health https://www.alzdiscovery.org/cognitive-vitality/blog/vegetar...
- netwanderer3 8y agoYou're right, I used to know a few vegetarians who often supplement their diets with Vitamin B-12 which theoretically could help boosting and balance their cognitive ability vs. meat eaters. I personally did not notice any cognitive problems in those people at least. Our DNA contains the sequence of folding steps instruction for each protein to fold. So for a protein to misfold itself, could this mean it must have received an incorrect instruction from the source? As we know, damages to DNA are often a result of foreign agents or coming from external environmental factors. Prevention is always better than a cure so it is probably a lot easier to figure out the source and eliminate that rather than trying to change the structure of these molecules which is extremely difficult.
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