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.
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.
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.
These are people who scour the internet looking for any information they can find and carefully read articles like this looking for a bit of hope that there may be a solution. But it’s bullshit. Don’t share these articles, for their sake.
I do not have, but I am personally affected, by this disease.
I appreciate your point, but this is one of the more interesting alternative hypotheses I've seen in the past ~8 years as an unwillingly-interested layperson.
Um, exactly? Science is the most visible journal after Nature, so it's the most competitive. "Insufficient page space" is exactly the same as "not impressive enough to be accepted".
we believe things only once we've exhausted our attempts to disprove it
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.
That's a personal heuristic - a very reasonable one, but it's still an argument from authority.
A fallacy assumes a cogent argument is being made. This is just a preference.
Whether you say "it must be true", or "it is likely to be true" does not matter. Credibility must only come from the statement itself and the evidence to support it.
However, while it is a logical fallacy, it is reasonable to temporarily hold beliefs for or against the truthfulness of a statement while no or insufficient evidence is present. As long as belief is not mistaken for proof, nothing is wrong about having such gut-feeling.
I think you are confusing deductive and inductive reasoning.
"The ad verecundiam fallacy concerns appeals to authority or expertise. Fundamentally, the fallacy involves accepting as evidence for a proposition the pronouncement of someone who is taken to be an authority but is not really an authority."
Stanford Encyclopedia of Philosophy (9):
Here we have a researcher who is an expert in the thing he's talking about. There are still absolutely reasons to be guarded-- the matter is not fully decided, it's just one study. Maybe this is an example of an ongoing controversy, and we're selectively ignoring other experts?
But it is different to extend a cautious benefit of the doubt here than it would be to take, say, Paul Rudd's word on the topic as final.
But for the rest of us, we have no choice but to trust authorities in some way when deciding how to interpret some new result.
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.
Instant throwback to 1997's Redneck Rampage game about US hillbillys..
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.
This is unsurprising, given the last two decades of drug trials targeting these molecules have all uniformly failed.
The alternative hypothesis is that these plaques are protective against neuronal infections that provoke alzheimers. That hypothesis has not garnered wide support yet, though it is growing, and is at least consistent with the inverse relationship observed.
Has there ever been any researches in determining the rates of Alzheimer disease in meat eaters vs. vegetarians?
"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)."
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.
There are enzymes, co-enzymes, and other molecules that can help a protein to achieve its proper shape.
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).
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.
Also by "factor" do you mean protein?
I'm just an electronics guy, would love to know more.
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 :-)
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
I suppose there is nothing saying that it can't be both be a prion disease, and enter the brain through a gingivitis path.
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.
With mad cow, will uninfected cow populations spontaneously develop mad cow on their own? Or was the first mad cow protein a rare misfortune not likely to happen again? Or did the first mad cow protein come from something other than a cow?
The protein structure needs to have a mutation which gives it a propensity to occasionally misfold. That creates a chain reaction.
If this happens at a low enough rate then the underlying protein may become widely distributed in the population, and then it may only take a chance mutation or misfold to cause the cascade
The reality is we don’t know what the prime mover in any of these conditions are. Likely some combination of random occurance and possibly some other mechanism as well. For example, CJD comes from mad cow - so mad cow is transmissible, but scrapie seems to both arise spontaneously in flocks and be transmissible between sheep
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.
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.
Well, unless you count physical exercise.
I like your mindset and I think your metaphor may be correct.
The distinction matters because the best treatment (greatest efficacy, most cost efficient) may target one or more of the links in the causative chain, but not necessarily the root cause.
Prevention can't, and to me Alzheimer's is something that should be prevented. But we work with what we have.
Some evidence the inflammation might be diet related too. Although I can't recall the source at the moment.
- 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.