[HN Gopher] New nanotherapy clears amyloid-b, reversing symptoms...
___________________________________________________________________
New nanotherapy clears amyloid-b, reversing symptoms of Alzheimer's
in mice
Author : self_awareness
Score : 194 points
Date : 2025-10-09 14:36 UTC (8 hours ago)
(HTM) web link (www.drugtargetreview.com)
(TXT) w3m dump (www.drugtargetreview.com)
| 317070 wrote:
| The paper: `Rapid amyloid-b clearance and cognitive recovery
| through multivalent modulation of blood-brain barrier transport`
| https://www.nature.com/articles/s41392-025-02426-1
|
| "Cognitive assessments revealed that treated AD mice exhibited
| significant improvements in spatial learning and memory, with
| performance levels comparable to those of wild-type mice. These
| cognitive benefits persisted for up to 6 months post-treatment."
|
| I'm curious if Derek Lowe will comment on this on his blog. I'll
| await his opinion on how much we ought to celebrate here. He's
| not a big fan of the amyloid hypothesis and has worked many years
| in this exact field, so I reckon he will point out why skepsis is
| warranted.
| underdeserver wrote:
| Yup. I hope he says something about what "nanotherapy" means.
| anon84873628 wrote:
| My biggest criticism of the article is emphasizing
| "nanotechnology" when it is really just an extra large
| synthetic molecule.
|
| I mean, it is nanotech! But just not the type most readers
| would imagine. They could have elaborated on an justified
| this better by explaining novel synthesis method or
| something.
| mattkrause wrote:
| (N+1)th time's the charm!
|
| I do sincerely hope that we find something for Azheimer's, but
| there's just a mountain of data suggesting that mouse models of
| Alzheimer's and/or ABeta simply not that useful.
| rob_c wrote:
| If it's the removal of the proteins not the plaque I wonder if
| that's the cause of people chasing the plaque for years? Classic
| correlation causation problem if so... Time to go read
| CrazyStat wrote:
| Amyloid plaques are protein.
| chc4 wrote:
| Wasn't it revealed that the research supporting amyloid-beta
| plaque as the cause of Alzheimer's was fraudulent?
| https://www.science.org/content/article/potential-fabricatio...
| https://www.science.org/content/article/alzheimer-s-scientis...
| epgui wrote:
| Yes, in a sense... but that doesn't mean amyloid-beta is an
| irrelevant therapeutic target. It's a bit more complicated.
| jvanderbot wrote:
| IIRC, it was revealed that treating this as a cause is wrong,
| it complicates or causes dementia, but is a symptom of
| something else, not a root cause of the disease.
|
| But treating symptoms, esp restoring cognitive function, is a
| good thing.
| p_j_w wrote:
| I'm not a neuroscientist, but it seems that hypothesis existed
| before that paper and has more supporting evidence than what's
| been retracted:
| https://en.wikipedia.org/wiki/Biochemistry_of_Alzheimer%27s_...
| mjamesaustin wrote:
| This therapy doesn't target the amyloid-beta plaques. It
| repairs the blood brain barrier, and then the body is able to
| clear away the plaques. Their buildup is a symptom of
| Alzheimers, not the cause.
|
| The problem with the amyloid-beta hypothesis was the assumption
| that these plaques were causing the Alzheimers and that
| removing them by itself could lead to a cure.
| lukeinator42 wrote:
| Exactly this. Amyloid-beta plaques and their association with
| dementia were discovered early on (late 1800s/early 1900s
| https://en.wikipedia.org/wiki/Amyloid_plaques#History), but
| the theory that they cause dementia hasn't panned out.
| matthewdgreen wrote:
| Whoa there. Is that what's happening? Cause an alternative
| theory is cause -> plaques -> cognitive disease. You seem to
| be arguing cause -> cognitive disease -> plaques, and I'm not
| sure this research demonstrates that. Does it?
| celrod wrote:
| I think they're arguing
|
| Cause -> cognitive disease Cause -> plaques
|
| That is, that the same cause is behind both.
|
| There may be some arrows from plaque to disease as well
| (i.e., that plaques also increase disease).
|
| I dont know the truth, but just trying to understand/follow
| Alzheimers news and reading comments.
| pessimizer wrote:
| Why does it seem like they're arguing that? I think that
| it's supposed to really be: cause -> (plaques = cognitive
| disease), and the fraud was (cause = plaques) -> cognitive
| disease.
|
| As I took it, understanding that there was a fraud doesn't
| mean that continually clearing the plaques wouldn't have a
| good chance of holding off cognitive disease indefinitely.
| matthewdgreen wrote:
| I'm simply arguing that the plaques could be the
| proximate cause and the problem addressed by this
| treatment could be the remote cause. The OP is being
| vague in the way they stated it, but it feels like
| they're saying the plaques are irrelevant. That doesn't
| seem to fit what we know: the evidence that cognitive
| symptoms are downstream of plaques is pretty compelling.
|
| I also don't think "fraud" should be used in this
| discussion at all.
|
| With all that said, if this One Weird Trick can
| clear/prevent the buildup of plaques (and thus the
| cognitive symptoms downstream of them), that's just a
| best possible outcome.
| JamesBarney wrote:
| I think amyloid being the proximate cause of neural
| degeneration in moderate and severe Alzheimers is basically
| disproven at this point.
|
| I still think it's more likely than not (70%) that it is a
| cause though farther upstream. There is a good amount of
| evidence tau is more likely the proximate cause due it more
| closely tracking disability in moderate to late stage
| Alzheimer's.
| anon84873628 wrote:
| While the article emphasizes the BBB repair aspect, it seems
| the treatment does ultimately target plaques directly at a
| mechanical level:
|
| >Normally, the protein LRP1 acts as a molecular gatekeeper,
| binding to Ab and transporting it across the BBB for
| elimination. In Alzheimer's, this system becomes fragile,
| leading to Ab accumulation. The supramolecular drugs mimic
| LRP1 ligands, binding to Ab and initiating its clearance,
| effectively resetting the system and restoring vascular
| function.
|
| My sense of the narrative is that "unclogging" the amyloid
| protein with this treatment allows innate repair functions to
| resume.
| shawnz wrote:
| Here's a good article which explains the remaining arguments in
| favour of the amyloid hypothesis:
| https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...
| amalcon wrote:
| It's most likely highly correlated, but not causative. That
| correlation still makes it diagnostically useful, which is how
| it's used here.
| tremon wrote:
| I thought amyloid-b buildup is usually determined at autopsy?
| That's not really the kind of diagnostic medicine I'm looking
| forward to. Can it also be determined via brain biopsy?
| mattkrause wrote:
| You can do PET imaging for it--there are a bunch of
| 18F-based tracers that work reasonably well. It also
| _inversely_ correlates with Abeta levels in the CSF. Ne
|
| Neither of those are particularly easy procedures, but
| certainly better than a biopsy (and autopsy!)
|
| https://pmc.ncbi.nlm.nih.gov/articles/PMC3264790/
| JamesBarney wrote:
| It's very likely causative. There is just too much evidence
| for it not to be. All the genes related to amyloid processing
| are correlated with Alzheimer rates.
|
| The most likely theory I've seen is amyloid causes tau
| buildup which leads to the majority of the damage. And by the
| time they give anti-amyloid drugs it's too late and the tau
| is doing the majority of the damage.
|
| An analogy would be if you have a hole in your house which
| leads to getting a rat infestation. Once you notice the rat
| infestation patching the hole isn't going to solve your
| problem. The hole caused you to get rat shit on your counter,
| but by the time you fix the hole it's too late to stop the
| rats from shitting on your counter.
| bitshiftfaced wrote:
| This article: https://www.astralcodexten.com/p/in-defense-of-
| the-amyloid-h... makes a pretty compelling argument for
| continued research on the link between amyloid-beta and
| Alzheimer's.
| matthewdgreen wrote:
| This article is incredibly informative and I wish the folks
| in this thread would read it. Doesn't make the current result
| any less exciting.
| JamesBarney wrote:
| There were some important papers that turned out to be
| fraudulent, but there is a large and broad body of knowledge
| supporting this link.
| JoshTriplett wrote:
| It's correlated, much as body temperature is correlated with
| infection. But much like lowering body temperature won't cure
| the infection, directly addressing the amyloid-beta plaques
| doesn't seem likely to directly address Alzhimer's. Addressing
| the actual root cause may _also_ make the plaques go away.
| anon84873628 wrote:
| FWIW the article says this:
|
| >"The long-term effect comes from restoring the brain's
| vasculature. We think it works like a cascade: when toxic
| species such as amyloid-beta (Ab) accumulate, disease
| progresses. But once the vasculature is able to function
| again, it starts clearing Ab and other harmful molecules,
| allowing the whole system to recover its balance. What's
| remarkable is that our nanoparticles act as a drug and seem
| to activate a feedback mechanism that brings this clearance
| pathway back to normal levels,"
|
| >...
|
| >Normally, the protein LRP1 acts as a molecular gatekeeper,
| binding to Ab and transporting it across the BBB for
| elimination. In Alzheimer's, this system becomes fragile,
| leading to Ab accumulation. The supramolecular drugs mimic
| LRP1 ligands, binding to Ab and initiating its clearance,
| effectively resetting the system and restoring vascular
| function.
|
| So we may be lucky in that addressing the plaques as a
| symptom does indeed (allow for) repair of the underlying
| cause. I guess the question is how long the benefit lasts.
| What triggers the negative feedback loop in the first place?
| The article claims long term improvement for the mice, which
| were genetically programmed for amyloid production. (So maybe
| not an accurate simulation of the root cause, but perhaps
| actually more of a steel man test.)
| perdomon wrote:
| This scandal comes to mind any time I see amyloid plaque
| research. Not sure if I misunderstood the scandal or if
| Alzheimer's research has too much momentum to pivot. My dad was
| diagnosed a few years back and seeing stuff like this is always
| encouraging and infuriating because of this science article.
| bpodgursky wrote:
| Fraudulent research should be treated as no-info, not a
| negative signal on the target. You can have fraudulent research
| supporting a correct theory. In fact this is more common,
| people will generally fake evidence to support a theory they
| think is probably true.
| btilly wrote:
| Yes, we have a mouse model of Alzheimer's that can be cured by
| preventing amyloid beta buildups. And billions of dollars in
| failed drug trials demonstrate that what works for those mice,
| doesn't work for humans.
|
| This has been demonstrated for many years. And yet we waste
| literally billions per year researching treatments that will only
| work in mice. And yet we regularly publish articles proclaiming
| that we can cure mice, humans are next!
|
| This research is BS and a waste of taxpayer money.
| jmount wrote:
| Isn't it often even worse in that many of the "models" are
| intentionally inflicting a condition superficially similar to a
| symptom, and then showing some treatment blocks or reverses
| that? So sometimes nothing to do with the underlying disease.
| btilly wrote:
| Yes, this is exactly the problem with animal models. We can
| tell that the animal has the same symptoms. We don't know
| that it has it through the same pathway as humans.
|
| The models have worked often enough that it is reasonable to
| hope that what works in animals, will work in humans. And it
| is easier to experiment on animals. This is why they are used
| in research.
|
| But when what works in animals doesn't work in humans,
| repeatedly, we should stop using that animal model in
| research.
|
| Here are examples of treatments for Alzheimer's that worked
| in animals, reached human trials, then failed to help humans:
| AN1792 (active Ab vaccine, Elan), Tarenflurbil
| (R-flurbiprofen), Semagacestat (g-secretase inhibitor),
| Bapineuzumab (anti-Ab mAb), Solanezumab (anti-Ab mAb),
| Crenezumab, ponezumab, gantenerumab, and BACE inhibitors
| (e.g. verubecestat, atabecestat).
|
| All of these were considered promising enough in mice to be
| worth expensive human trials. Where they failed. Those
| weren't cheap failures, either.
| nradov wrote:
| The NIH recently changed their grant funding policy to focus
| more on human experiments instead of animal models. It will
| take some years to see whether this change has any positive
| or negative effects.
|
| https://grants.nih.gov/news-events/nih-extramural-nexus-
| news...
| pbasista wrote:
| In general I do not think that a research which does not lead
| to a full resolution of the primary issue can be dismissed just
| because it does not actually resolve the issue.
|
| Every step of the way towards the resolution of the issue is
| important. Even ruling out what does not work is important.
|
| Without those incremental advancements, we may never reach the
| end goal.
| btilly wrote:
| Of course we should try to learn from past research.
|
| But sometimes the lesson to be learned is that what we were
| is a bad approach, and we need to rethink things. We can't
| simply run experiments and get results. We also need to study
| whether our experiments are telling us what we think that
| they are telling us. Because if we don't know what our
| experiments are actually telling us, we're going to
| misunderstand the results.
|
| https://people.cs.uchicago.edu/~ravenben/cargocult.html is
| worth a read on this. Among other examples, it includes an
| explanation of what actually has to be done in order for a
| rat running a maze to actually test the rat's memory. And how
| it is that we know that this is what has to be done.
|
| The fact that psychologists ignored that experimental
| procedure marked psychology as a cargo cult science. (Some 40
| years later, the replication crisis forced psychologists to
| at least talk about the issues that Feynman raised...)
|
| The fact that we continue testing animal models of
| Alzheimer's that we have proven to be a bad model of humans,
| likewise shows that Alzheimer's research has become a cargo
| cult science.
| BriggyDwiggs42 wrote:
| Okay but how exactly should researchers come up with drugs to
| try on humans then?
| btilly wrote:
| This argument is like the infamous drunk who was arguing that
| he should continue looking for his keys under the street
| light, because the place where he actually dropped them had
| no light so he couldn't see.
|
| At this point it is a waste of time and money to produce more
| drugs that are guaranteed to fail in humans. Making it harder
| to waste time and money in this way is a feature, not a bug.
|
| After we have better basic science about what likely causes
| Alzheimer's, we can go back to the question of how to find
| drugs that might help. Trying to do it in the other order is
| putting the cart before the horse.
| maybelsyrup wrote:
| The litany of posts you've made in this thread indicate
| that you're passionate about this topic.
|
| Sincere question: wouldn't the great energy and intensity
| you're putting into web forum replies be better channeled
| into Alzheimer's advocacy?
| mattkrause wrote:
| There are other animal models, some of which even seem to
| develop dementia-like symptoms spontaneously.
|
| Mice have absolutely dominated research because they're
| relatively cheap, lots of powerful genetic tools are
| available, and the PR is more tractable. However, that
| doesn't mean they're the right choice for every experiment.
| stickfigure wrote:
| Perhaps you would like to volunteer as a test subject instead?
| pinkmuffinere wrote:
| That wouldn't work, the test subject needs a brain.
|
| (Sorry, this is a rude joke. Truthfully my disagreement with
| patent is only medium-strength. I just can't resist jokes.)
| psygn89 wrote:
| Are you a dad by any chance?
| pinkmuffinere wrote:
| No, but I have nothing against them. Hell, I'm half dad
| on my father's side! :D
| btilly wrote:
| This is a nonsequitur and an ad hominem.
|
| Did you have a substantive response? Or are you just here to
| deliver meaningless snark?
| stickfigure wrote:
| It is neither non sequitur nor ad hominem. Look those up
| (or ask chatgpt to do it for you).
|
| But in case it isn't clear: All models are inherently
| imperfect. That doesn't mean they aren't useful. The ideal
| test subject tends to complain when you propose dissecting
| their brain for analysis.
| btilly wrote:
| I will not bother to respond to you again.
|
| Instead I will trust that those in the audience that I
| might care about, can judge your lies and insults
| correctly.
| biophysboy wrote:
| Billions of dollars leading to failure during clinical trials
| is the overwhelmingly likely outcome for all therapeutic areas,
| particularly so for CNS.
|
| Somebody else asked "what is your alternative?" and you
| responded with "drunk under a streetlamp". The issue with this
| is that all of science is drunks under streetlamps. Scientists
| rely on a set of methods; for preclinical work, this is animal
| models, organoids/tissue chips (still in development), and in-
| silico AI stuff. Slim pickings! To use your lamp analogy, all
| of these options will give off a pretty dim amount of light.
| btilly wrote:
| What evidence would it take for you to reconsider how we are
| approaching Alzheimer's?
|
| Our working theory is that amyloid beta plaques cause
| Alzheimer's, and so preventing them will prevent the disease.
| We have absolutely demonstrated our ability to prevent those
| plaques in both mouse models and humans. Doing this cures
| symptoms in mouse models. It does not cure symptoms in
| humans. I already gave a list of 9 different approaches that
| generated this exact result. How many more billions do we
| need to spend on new approaches to do the same thing, before
| the field reconsiders the theory?
|
| And the failure here is not just with failed drug trials. In
| this century, it is easier to find fraudulent data advancing
| the hypothesis, than real data. With the result that several
| fraudsters have managed to create very good careers for
| themselves before being caught. This is a sign that there is
| something very deeply wrong with the field, if such fraud is
| rewarded rather than being caught more promptly.
|
| Furthermore you are absolutely wrong about what I said about
| the alternative. My drunk under a streetlamp comment was
| about continuing to use these animal models to create more
| drugs. My suggested alternative was basic science. If amyloid
| beta plaques are a symptom, not a cause, of Alzheimer's, then
| what is the cause? We need to figure that out, before trying
| to create new drugs for it.
|
| And it isn't like basic research has nothing to try.
| Alternate hypotheses with some suggestive data for them
| include Tau folding, inflammation (possibly caused by
| viruses), problems with the blood-brain barrier, problems
| with the mitochondria of neurons, dysregulation of metal
| ions, and so on. Maybe the real answer is not even on this
| list. But finding and demonstrating the real cause should be
| a high priority.
|
| My father-in-law has Alzheimer's. If research continues for
| the next 30 years like it has in the last 30 years, there
| will still be no treatment when my wife gets old enough to
| worry about getting it. This is not a potential future that
| I'm particularly looking forward to. (But maybe I'll get
| lucky and get it before her...)
| biophysboy wrote:
| All of those alternative hypotheses have been investigated
| with mice
| didibus wrote:
| > then what is the cause? We need to figure that out,
| before trying to create new drugs for it.
|
| Isn't that what the animal experiments are for? Trying to
| find causation?
| yxhuvud wrote:
| Research into medicine that make the blood/brain barrier
| function like on healthy people will certainly find
| applications though, regardless of if it is useful against
| Alzheimers though.
| alphazard wrote:
| > Instead of targeting neurons directly, this method focuses on
| repairing the blood-brain barrier (BBB), the brain's defence
| against harmful substances. By restoring proper BBB function, the
| researchers achieved a reversal of Alzheimer's pathology in
| animal models.
|
| Alzheimer's patients often respond positively to exogenous ketone
| esthers, and a ketogenic diet. The proposed mechanism for this is
| that ketones are transported across the BBB differently than
| glucose. Even if glucose is unable to be transported into the
| brain, ketones often still are. Now that there is a drug to
| repair the BBB, and likely glucose transport as well, I expect
| the funding will mysteriously show up to properly investigate the
| "brain diabetes" theory of Alzheimers.
| GenerWork wrote:
| >I expect the funding will mysteriously show up to properly
| investigate the "brain diabetes" theory of Alzheimers.
|
| There was the SNIFF [0] study that delivered insulin via nasal
| spray, so there's already some funding and studies happening.
|
| [0] https://www.clinicaltrials.gov/study/NCT01767909
| JumpCrisscross wrote:
| > _Now that there is a drug to repair the BBB (and likely
| glucose transport as well), I expect the funding will
| mysteriously show up to properly investigate the "brain
| diabetes" theory of Alzheimers_
|
| Why is this cast as conspiracy versus a natural consequence of
| risk and incentives? ('Brain diabetes' is in no way a neglected
| avenue of Alzheimer's research.)
| matthewdgreen wrote:
| There's been a long-running Internet movement to cast the
| beta-amyloid and beta-amyloid/tau hypotheses as an evil plot
| by scientists to siphon money away from research that works.
| It's a whole thing. I anssume it's because Alzheimer's
| legitimately sucks (my mom has it) and that means there has
| to be someone we can blame.
| smt88 wrote:
| Wait, but isn't that "conspiracy" literally true? People
| faked data and everything...
|
| https://hn.algolia.com/?dateRange=all&page=0&prefix=true&qu
| e...
| alphazard wrote:
| > There's been a long-running Internet movement to cast the
| beta-amyloid and beta-amyloid/tau hypotheses as an evil
| plot by scientist
|
| No one was twirling their mustache trying to make people
| suffer. Someone had a lab, and prestige and control over
| funding and the best way to keep it all was by being
| dishonest. That negatively affected progress in the field.
| You can call it "evil" if you want, but more objectively it
| was unaligned incentives. The corruption was covered in
| mainstream news, it's not a conspiracy theory. Since the
| scandal got out, the speed of progress has improved
| significantly.
| KPGv2 wrote:
| > No one was twirling their mustache trying to make
| people suffer. Someone had a lab, and prestige and
| control over funding and the best way to keep it all was
| by being dishonest.
|
| The second sentence and the first sentence are merely
| literal and figurative descriptions of the same activity.
|
| Also, for this to be true, it has to mean lab workers
| knew about progress but fucked over their own family with
| Alzheimers. And it has to mean _every single one of them_
| did this.
|
| *Edit* Actually there's another way to interpret what you
| wrote. My mistake. I imagined a scenario where someone
| knew of progress and was dishonest by hiding it, but you
| might've been alluding to someone knowing an avenue _wasn
| 't_ fruitful but was dishonest by making it seem more
| fruitful.
|
| I think the latter is easier to hide than the former
| since it doesn't require directly fucking over your
| family, merely very indirectly by siphoning off a
| fraction of total funds to be flushed down the toilet.
| feoren wrote:
| The latter is what happened, for upwards of ten years.
| And it wasn't a small fraction of the funding -- almost
| no funding was allocated to any research not looking at
| amyloid plaques, because the intellectual giants'
| (falsified) research was showing that that was by far the
| most promising avenue to explore.
| matthewdgreen wrote:
| Again, there were a couple of instances of fraud in one
| sub-branch of a sub-branch of a field ages ago, and The
| Internet has decided to turn it into a conspiracy theory.
|
| On the off chance that you're actually a decent, honest
| person, I urge you to actually go learn about this theory
| that you're promoting. Go out and actually figure out the
| truth, because if it turns out that you're wrong about
| the impact and intentions, you're helping to harm a lot
| of people.
| feoren wrote:
| > You can call it "evil" if you want
|
| It was a concerted and intentional effort to fake data
| and falsify research into a pervasive deadly disease,
| specifically in order to hoard funds going to research
| they knew was, if not a dead end, at least not nearly as
| promising as they were claiming, preventing those funds
| from going to other research groups that might actually
| make progress, essentially _stealing donations from a
| charity_ , and using their power and clout to attack the
| reputations of anyone who challenged them. They directly
| and knowingly added some X years to how long it will take
| to cure this disease, with X being at least 2 and
| possibly as much as 10. When Alzheimer's is finally
| cured, add up all the people who suffered and died from
| it in the X years before that point, and this research
| team is _directly and knowingly responsible_ for all of
| that suffering. Yes, I think I will call it absolutely
| fucking evil.
| matthewdgreen wrote:
| Again, I urge you to read this article and stop promoting
| conspiracy nonsense. I take this very personally because
| my mom has this disease, and people who _clearly don 't
| understand what they're talking about_ fuming about
| conspiracies really doesn't help anyone, and probably
| hurts them immeasurably.
| https://www.astralcodexten.com/p/in-defense-of-the-
| amyloid-h...
| andrewmcwatters wrote:
| If that's not evil to you, everything wrong in your world
| must just be misaligned incentives.
| matthewdgreen wrote:
| I really urge you to read this article. It was posted
| elsewhere in the thread as well:
| https://www.astralcodexten.com/p/in-defense-of-the-
| amyloid-h...
| alphazard wrote:
| I can't guess what point you're trying to make with a
| long article that acknowledges the fraud in the
| beginning, and then rehashes the initial reasons for
| looking into the amyloid hypothesis. No one is claiming
| it was stupid to look into the amyloid hypothesis. They
| are complaining that it hasn't been the most promising
| theory in quite a long time, and it was fraudulently held
| as the most promising. Other theories, arguably more
| promising, are listed throughout your article.
|
| There is a testable prediction in your article.
| Unfortunately, I don't think the mechanism is quite
| restricted enough. TFA says that repairing the BBB helps
| amyloid plaque clearance. Would the author of your blog
| post claim that as a win, or admit that the plaques are
| downstream of the problem, and that BBB integrity is
| closer to the root cause of the disease process?
| mrguyorama wrote:
| It's a whole thing because there's been over a century of
| concerted effort in the US to cast _all of science_ as an
| evil plot.
|
| The Discovery institute, and all their donors and
| connections (including literal politicians) tell millions
| of children that science is a plot of satan to make you
| doubt god.
|
| The people who created the Scopes "monkey trial" never went
| away, are fabulously well funded and organized and
| connected, and _have succeeded beyond their wildest dreams_
|
| Now they are trying to expand that belief to all of
| academia, so that people who never set foot in an academic
| institution and have never tried any higher education
| beyond high school and have _never even attempted to read a
| scientific paper_ are convinced that all Academics are in a
| concerted plot.
|
| 30 million Americans claim to believe God created humans
| exactly as they are now within the past 10k years.
|
| That's the _low estimate_ of christian fundamentalism and
| science hostile cohort in the US.
| ashtakeaway wrote:
| The science hostile cohort is flourishing wherever
| christian fundamentalism is rampant, in some places most
| people are exactly this. A lot of the depressing things
| Carl Sagan mentioned in Demon Haunted World turns out to
| be true. I had thought that 20 years ago we were on our
| way to being a rational society but it turned out this
| notion was on its way out.
| regnull wrote:
| When you say "science", you need to distinguish between
| science as philosophy vs. science as an institution.
| Science as philosophy is a way of thinking - an attempt
| to understand knowledge and reality. The science as an
| institution on the other hand has all the imperfections
| as any other institution, since the people in charge are
| driven by self interest and not just the search for the
| truth. So, when you say the people distrust science, it
| seems bizarre that they doubt science as philosophy,
| while in fact they doubt the institution. It's perfectly
| fine to mistrust the institution. If you want to consider
| a few failures, just in the recent years, I have some for
| you:
|
| - Hungarian-born biochemist Katalin Kariko, who developed
| the key mRNA modification that enabled effective COVID-19
| vaccines, was repeatedly denied grants and demoted during
| her career. She and her collaborator, Drew Weissman,
| struggled for years to gain recognition and funding for
| their work [1]
|
| - On the other hand, the Wuhan Institute of Virology had
| no trouble getting grants from NIH [2]
|
| - Surgeon General Jerome Adams was saying that masks are
| not effective against Covid [3]
|
| - Social distancing was of supreme importance, until it
| turned out that it's fine not to distance if it's for a
| good cause [4]
|
| [1] https://www.statnews.com/2022/02/01/kariko-problem-
| lessons-f...
|
| [2] https://www.bmj.com/content/382/bmj.p1701
|
| [3] https://www.npr.org/sections/health-
| shots/2020/07/01/8862991...
|
| [4]
| https://www.politico.com/news/magazine/2020/06/04/public-
| hea...
| ToucanLoucan wrote:
| > So, when you say the people distrust science, it seems
| bizarre that they doubt science as philosophy, while in
| fact they doubt the institution.
|
| The vast, vast, vast majority of the Christian
| fundamentalists whom are the backbone of this movement
| and the subject of this discussion do not distinguish
| between these things. They do not distrust "big science,"
| they distrust science, full stop. The fact that science
| as an institution is subject to the same corruptive
| forces as every other institution is a convenient post-
| hoc rationalization for the belief they already had and
| wanted to justify, just like a lot of other post-hoc
| rationalizations they have for other beliefs they have.
| They dislike science _now_ because they are told to by
| their ministers, no more reason than that, and we know
| this because science and their religion coexisted
| peacefully and uneventfully for centuries until it become
| inconvenient for a segment of the church 's politics.
| Excluding of course Gallileo, and for the same reasons.
|
| Science (both as philosophy and institution) gets it
| wrong, but has built-in mechanisms that correct those
| issues. Eugenics was discredited by science. Andrew
| Wakefield's bullshit autism study was discredited by
| science. Religion gets it wrong and then calls it
| mystery.
|
| It's especially ironic to hear institutional corruption
| invoked as a critique of science, when many of the
| loudest voices in this conversation come from religious
| institutions that have spent decades shielding their own
| leadership from accountability for far more egregious
| abuses.
| greenchair wrote:
| effective covid vaccines?
| stinkbeetle wrote:
| The bigger problem and the one that is more damaging to
| public trust in science is actually politicians (and
| bureaucrats and other government and non-government
| institutions) who spread disinformation that policy is
| science. Their policy is "based on the science" they will
| claim, and therefore to disagree with their policy is to
| be a "science denier" they assert, without evidence.
| These dishonest interests essentially hijack the good
| name of science by fooling low information voters.
|
| There is a lot of science around epidemiology, virology,
| vaccines, and medicine. There is no evidence based
| scientific consensus that it was the "correct" policy to
| shut down large parts of the economy, subsidize
| mothballed businesses, admit COVID positive patients to
| nursing homes, impose emergency policies impinging on
| human rights like restricting travel and association and
| medical autonomy, or fast-track vaccines for COVID.
|
| You could argue for those policies, but it should have
| been completely reasonable to argue against them. That
| does not make you "anti-science". People can and should
| question the efficacy of the vaccines, and the lies that
| were repeated by certain "news" corporations and
| politicians who had interests in and donations from
| pharmaceutical companies, with fantastical claims about
| them that turned out to be false. That does not make you
| "anti-science" either.
|
| Similar thing with the science of greenhouse gasses and
| global warming. There is a lot of science around the
| fundamentals of those mechanisms, there is a lot of
| science showing that warming can gravely damage
| ecosystems and human societies and therefore limiting
| human CO2 emissions would be a benefit. That's great,
| that is science. What is not science is any particular
| government policy purported to help this. Proposing to
| reduce or tax GHG emissions in one country and thereby
| incentivize production in another country (with far
| higher emissions intensity of production) is not
| "science". It's not "anti-science" or "climate denier" to
| question or disagree with a policy like that, for
| example.
| overgard wrote:
| I've heard the colloquial phrase "type 3 diabetes" appear a lot
| in talk about Alzheimers, so I'd be shocked if there isn't a
| lot of research going into that. I just read a book about how
| metabolism is related to a lot of mental disorders (depression,
| schizophrenia, etc.) so I think it's something that's
| definitely being looked at (the book is called Brain Energy, I
| think).
| Mabusto wrote:
| Hey what was the book out of curiosity?
| ajross wrote:
| > Alzheimer's patients often respond positively to exogenous
| ketone esthers, and a ketogenic diet.
|
| I went looking for a cite here and came up almost empty
| (wikipedia has one link to an 11 year old paper that doesn't
| really say much authoritative in the abstract).
|
| I wish people would be more rigorous about this stuff.
| Atkins/paleo/keto is the gluten-free/hemp/cbd/hippy magic of
| the hacker set, not least because it's nearly perfect wish
| fulfillment[1]. And it appears in a lot of mystical contexts
| too, showing up as a cure for whatever is being discussed.
|
| The actual science, every time I look, is a _lot_ less
| convincing.
|
| [1] Meat! It's all meat! We love meat!
| motoboi wrote:
| Maybe you can see this as more compelling evidence:
| https://consensus.app/search/does-ketonic-diet-improve-
| alzhe...
|
| >Cognitive Effects and Clinical Outcomes > >Multiple
| systematic reviews and clinical trials report that ketogenic
| diets (KD) or ketone supplementation can lead to improvements
| in cognitive function, daily living activities, and quality
| of life in people with mild-to-moderate Alzheimer's disease
| 413141819. Chronic KD interventions (3-4 months) have been
| associated with increased cognitive test scores and improved
| memory performance 1418. Some studies also show positive
| changes in Alzheimer's biomarkers, such as reduced tau and
| increased amyloid-beta 42 in cerebrospinal fluid 7."
| ajross wrote:
| Well, thanks. That's certainly better than what made it
| into wikipedia. But honestly: no? Only 41% of papers
| answering "yes" to an engaging and evocative hypothesis, in
| the era of the replication crisis, and _especially_ after a
| decade and a half of the hypothesis sitting around in
| general lore, generally means "no, duh" in my experience.
|
| As the site itself says, "evidence is still limited and
| more research is needed", which is definitely not
| "compelling". My money still sits on "nerd wish
| fulfillment". But we'll see.
| motoboi wrote:
| Yeah, there are studies suggesting neurons, far more so
| than many peripheral cells, are especially vulnerable to
| insulin resistance. So by the time you see systemic
| insulin resistance by standard measures, the brain may
| already be slipping. I suppose this is why ketonic diet
| has any role in restoring cognitive function.
| m0llusk wrote:
| The idea that paleo/keto is all buttered meat is strange and
| fairly recent, with wish fulfillment probably being strongly
| involved. Meat would have been a luxury not available for all
| meals so other tissues like tendon, tripe, and skin would
| have been common ingredients. That plus other changes like
| boiling most meals and serving them with the boil water make
| a huge difference in the nutritional profile.
| ajross wrote:
| > The idea that paleo/keto is all buttered meat is strange
| and fairly recent
|
| To be clear: the dietary theories here (such as they are)
| are surely rigorously defined and subsume all sorts of
| choices for how to get fats and avoid carbs.
|
| But to a person, every solitary practitioner I've ever met
| has implemented their Atkins/paleo/keto diet with almost
| exclusively meat.
|
| It's a MEAT! diet because nerds love MEAT!.
| timschmidt wrote:
| I read "Prolonged Meat Diets with a Study of Kidney
| Function and Ketosis" by Walter S. McClellan and Eugene
| F. Du Bois, Journal of Biological Chemistry (1930). The
| original paper that kicked off all the Atkins diet ideas.
| It made quite a point of the fact that the two men
| participating started off thinking that they'd like
| eating all meat, and quickly realizing that they began
| craving fat and organ meat to an extent that it ended up
| making up the majority of their diet.
| epicureanideal wrote:
| Would it be possible to artificially increase the glucose in
| the brain to get a nootropic effect?
| 1970-01-01 wrote:
| Why isn't "in mice" an automatic flag for posting? This is not a
| breakthrough in Alzheimer's nor is it headline news in
| Alzheimer's research.
| bookofjoe wrote:
| I asked this question in Ask HN about six months ago but
| received little support and much criticism.
| DaveZale wrote:
| from the bbb wiki:
|
| There is also increasing evidence that a healthy gut microbiome
| is necessary to maintain BBB integrity, both in development and
| aging.[38][39][40][41]
|
| I'll drink to that (kefir)!
| sys32768 wrote:
| I think the main progression is lymphatic dysfunction > chemical
| build-up > BBB damage > neurodegenerative plaques and tangles.
|
| My mother died from Alzheimer's at 77 but was the picture of
| health and happiness for many years prior, but never slept well
| to the point she had to have her own room away from Dad for many
| years.
|
| Maybe the trick is going to be repairing the BBB and stimulating
| lymphatic function rather than chasing down every factor that
| explains why the BBB and/or lymphatic function is compromised in
| the first place.
| JamesBarney wrote:
| I think the cure is going to be something that dissolves tau
| tangles, or something safe enough we can give as a preventative
| to people 10-20 years before they develop symptoms that helps
| with amyloid.
| anon84873628 wrote:
| The authors of this work believe the treatment enables BBB
| repair and restoration of healthy vasculature.
| BenFranklin100 wrote:
| People are criticizing mouse models of AD. There is
| understandable given the confusion of the roles of animals models
| in disease. Let me explain:
|
| First, the very name, 'animal model of disease" is misnomer, and
| the cause of most of the confusion. Animal models are more
| accurately described as 'models of mechanism'.
|
| Second, while mouse are different from humans and how a disease
| manifests is different as well, many of underlying mechanisms
| that drive a disease share strong similarities across species.
| Mice, rats, dogs, pigs, humans etc... all share the same
| fundamental building blocks and cellular/tissue/organ mechanisms.
| Studying how a disease or even partial aspects of a disease
| manifests in, say, a mouse, can offer extraordinary insights in
| how the disease may manifest in humans. This can provide a strong
| experimental basis for potential therapies in humans. (A rough
| analogy is the field of software is that different programs can
| use the same functions. Understanding how a function is
| misbehaving in a simple program can provide insights in how it is
| misbehaving in a more complex program.)
|
| Third, many diseases are difficult or impossible to study in
| humans. Alzheimer's is a good example as the progression occurs
| on a timescale of decades. Further, we obviously can't go around
| cutting out brain tissue from live humans.
|
| It's a big topic, but hopefully my brief outline provides some
| context for the use of animals models. We scientists also use
| cell and organoid models, which, while lacking key details of
| animal models in unknown ways, can provide insights as well.
| dsign wrote:
| If the causal mechanism in Alzheimer's is not clear, what's to
| say it isn't about 20 or 20000 different things going wrong in
| ways and proportions which are very specific to each individual?
|
| I'm not criticizing basic research, which I consider immensely
| useful. Rather, the way we expect for it to become magical drugs.
| The peak of contradiction is posing that humans are inscrutable
| creations of God who wills us to age and die miserably, and in
| the same breath also wanting to have a neat repair handbook
| indicating fixed doses of the same drugs for each symptom--as if
| we were some cheap car model that comes without spares nor OBD
| port, and that it's only serviced at the end. I think we need to
| solve that.
| w10-1 wrote:
| > what's to say it isn't about 20 or 20000 different things
| going wrong
|
| In this case, the therapy resulted in old mice performing like
| young mice (in addition to the amyloid-beta level reducing).
| anon84873628 wrote:
| Well they synthesized a magic molecule that mimics an
| endogenous compound that stops functioning in the diseased
| systems.
|
| Everyone agrees with you. The whole era is "precision
| medicine".
| Rikudou wrote:
| For one hundredth goddamn time: Mice don't have Alzheimer's. They
| can't ever get it and almost none of the successes scientists
| achieve with the mice illness _that has nothing to do with
| Alzheimer 's except similar symptoms_ are reproducible in humans
| at all.
|
| I really wish the news sites would get it correctly from time to
| time, this is misleading as hell.
| gcanyon wrote:
| > The researchers tested their approach in mice genetically
| programmed to overproduce Ab and develop cognitive decline
| similar to Alzheimer's pathology.
|
| Thoughts on that FTFA?
| rippeltippel wrote:
| Original article was posted on HN:
| https://news.ycombinator.com/item?id=45508672
| chermi wrote:
| The headline really, really annoys me. It makes it sound causal,
| amyloid-B removal causes reversing symptoms of alzheimer's. Thus
| supporting and even making seem certain the still somehow
| overwhelmingly popular (not to sound like conspiracy anti-pharma
| guy(1)) amyloid theory of alzheimers.
|
| All this shows is that _one_ of the effects of the treatment is
| clearing aggregates, _IN MICE_. That 's it, nothing more.
|
| We don't know for sure the causal mechanism. There was/is a
| fanatical well-funded machine behind the amyloid hypothesis; that
| doesn't make it correct. There is much reason to doubt it or at
| least downgrade it to a contributing but not sole causal
| mechanism.
|
| (1) it is absolutely mind-boggling to me that the amyloid
| clearing drugs like Aduhelm got FDA approval while so many much
| more proven treatments for other diseases sit waiting.
| wewewedxfgdf wrote:
| Mice get all the big health discoveries.
|
| We're going to be ruled be a race of super healthy, immortal,
| super intelligent lab mice.
| jasonvorhe wrote:
| Nah, we just love torturing and killing animals for science.
| DaveZale wrote:
| From 2023: It has been suggested that the BBB breakdown may
| precede cognitive decline and neurodegeneration, highlighting the
| critical need for further exploration of the BBB's role in AD and
| its potential as a therapeutic target [22]. The BBB endothelium
| is a specialized system of brain microvascular endothelial cells
| that separate circulating blood from the brain's extracellular
| fluid, maintaining the brain's homeostatic environment [23]. The
| BBB endothelium plays a crucial role in the protection and
| functioning of the brain, allowing the selective passage of
| nutrients and molecules essential for brain function while
| simultaneously preventing the entry of potentially neurotoxic
| substances [22].
|
| Also interesting: the two-hit vascular hypothesis of AD suggests
| cerebrovascular damage (hit 1) as an initial insult that is self-
| sufficient to initiate neuronal injury and neurodegeneration.
| Additionally, it promotes the buildup of Alzheimer's Ab toxin in
| the brain (hit 2)
|
| https://pmc.ncbi.nlm.nih.gov/articles/PMC10671257/
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