Proteins central to the pathology of Alzheimer’s disease act as prions

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#81

Post by arcticbull » Thu, May 02, 2019, 2:09 PM UTC

mikeash wrote: post #78

arcticbull wrote: post #50

Earlier quoted context omitted.

Parent is right this is an appeal to authority. It doesn’t make it more or less right whether a Nobel prize winner comes up with the idea or my mom does, we need to evaluate it on its merits alone. The corollary as I mentioned in a sibling post is that when you have a hammer everything starts to look like a nail.

We rely on a million appeals to authority every day of our lives. Try some new food, trusting that it won’t kill you because somebody says it won’t, and nobody bats an eye. Say you give more weight to a study performed by an expert, when that has no immediate bearing on your life, and everybody loses their mind.

Well said. Myself specifically, I'd like to think science is supposed to be better than that -- neutral, dispassionate. It probably isn't because it's done be humans, but I want it to be.

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#82

Post by Cosi1125 » Thu, May 02, 2019, 2:30 PM UTC

bboygravity wrote: post #73

Cosi1125 wrote: post #69

Earlier quoted context omitted.

Or, you know, it might be that Alzheimer's has an autoimmune factor contributing to it... :-)

Can 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.

Sure! 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

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#83

Post by betenoire » Thu, May 02, 2019, 2:31 PM UTC

theprotocol wrote: post #64

peteretep wrote: post #52

Earlier quoted context omitted.

> that's an argument from authority rather than one of science though. No. An appeal to authority would be "this must be true because someone authoritative said it". Saying "I am willing to treat this claim more credibly than other claims because the source is credible" is not a logical fallacy.

>"I am willing to treat this claim more credibly" That's a personal heuristic - a very reasonable one, but it's still an argument from authority.

A heuristic is a bias, not a fallacy. "All else equal, I'll try this path first".

A fallacy assumes a cogent argument is being made. This is just a preference.

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#84

Post by dekhn » Thu, May 02, 2019, 3:05 PM UTC

cjbprime wrote: post #14

Y'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…

senior author of the article was the person who established that prions are a legitimate disease caused by protein folding he had to fight an uphill battle for over 20 years to get his ideas established so I'm going to actually give him a ton of credit and the ability to publish what he wants to because he's already demonstrated he's responsible. He also won the Nobel prize for that work.

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#85

Post by dekhn » Thu, May 02, 2019, 3:07 PM UTC

8note wrote: post #48

autokad wrote: post #39

Earlier quoted context omitted.

one of the authors discovered prions, so I am not so quick to discount their work.

that's an argument from authority rather than one of science though. we believe things only once we've exhausted our attempts to disprove it

The important context here is that the author spent 20 years fighting The Establishment over the facts of prions and ultimately was proved completely correct. that makes him the ultimate authority in this case because he had to actually fight to overturn a long-standing scientific belief with heroic data collection and a hostile environment

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#86

Post by achenatx » Thu, May 02, 2019, 3:16 PM UTC

fjfaase wrote: post #76

netwanderer3 wrote: post #65

Earlier quoted context omitted.

You'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 re…

As I understand it, the DNA only contains the sequence of amino-acids from which the protein is built, not their folding instructions. Some proteins are also modified and/or cut in pieces by other proteins before reaching a functional state. Discovering how a protein folds, is a very complex problem, that would have been much easier if it were indeed encoded by the DNA. the website https://fold.it/portal/ gives a goo…

My biochemistry education is 20 years old.. As you say DNA encodes the sequence of amino acids. Protein folding is a thermodynamic problem as parts of the protein stick to other parts and bonds try to achieve a low energy shape.

There are enzymes, co-enzymes, and other molecules that can help a protein to achieve its proper shape.

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#87

Post by dekhn » Thu, May 02, 2019, 3:26 PM UTC

thaumasiotes wrote: post #19

cjbprime wrote: post #14

Y'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…

> 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.

Here'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.

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#88

Post by dekhn » Thu, May 02, 2019, 3:27 PM UTC

arcticbull wrote: post #49

traek wrote: post #42

Earlier quoted context omitted.

Sure, but this particular study came out of the lab of the Nobel-prize-winning scientist who literally discovered prions. I think it's at least worthy of discussion.

You know what they say, when you’ve got a hammer everything looks like a nail. I’m an armchair physician at best, and I’d say that this doesn’t disprove the viral infection thesis at all. That amyloid and tau act as prions isn’t really relevant if they’re in fact produced initially in response to an infectious agent in an attempt to stop its spread. I’d suggest this is particularly likely to be true as attempts to cl…

plaques are proxies of disease, not disease-causing or necessarily harmful in themselves.

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#89

Post by dekhn » Thu, May 02, 2019, 3:29 PM UTC

arcticbull wrote: post #50

8note wrote: post #48

Earlier quoted context omitted.

that's an argument from authority rather than one of science though. we believe things only once we've exhausted our attempts to disprove it

Parent is right this is an appeal to authority. It doesn’t make it more or less right whether a Nobel prize winner comes up with the idea or my mom does, we need to evaluate it on its merits alone. The corollary as I mentioned in a sibling post is that when you have a hammer everything starts to look like a nail.

I have to strenously disagree on this point. In this case, the author won the Nobel Prize after fighting the establishment for 20 years over a basic idea- that a disease could be caused by misfolded proteins and that the proteins can themselves cause more proteins to misfold in a cascade- ultimately showing that his theories were correct.

When a person fights the establishment and shows their data and ultimately gets accepted and defines the new paradigm, they've earned a seat at the table to speculate on how things work. They proved their worthiness as an authority.

That doesn't mean we shouldn't evaluate on the merits, but the priors are very heavily in his favor.

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#90

Post by cjbprime » Thu, May 02, 2019, 3:29 PM UTC

dekhn wrote: post #84

cjbprime wrote: post #14

Y'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…

senior author of the article was the person who established that prions are a legitimate disease caused by protein folding he had to fight an uphill battle for over 20 years to get his ideas established so I'm going to actually give him a ton of credit and the ability to publish what he wants to because he's already demonstrated he's responsible. He also won the Nobel prize for that work.

You could modify your belief in his authority based on the fact that this result was presumably rejected by top-tier journals, and probably for non-trivial reasons. I don't know anything about the field so I can't say whether that's appropriate here. But if you're willing to grant credence based on a prior Nobel, you should be willing to consider taking some away based on the publishing journal's reputation. Why wouldn't a top-tier journal want to publish a Nobel winner's Alzheimer's breakthrough?