24 ms·

Alzheimer’s amyloid hypothesis ‘cabal’ thwarted progress toward a cure (2019)

• purplepatrick 4y ago
  Yes… That’s how all of science works (minus the cabal). Thomas Kuhn’s 1962 classic “The Structure of Scientific Revolutions” is about this dynamic…
• ray__ 4y ago
  It is easy to discount the amyloid hypothesis and amyloid research based on the facts that 1) amyloid is not required for neurodegenerative disease pathology, 2) many people who do harbor amyloid fibrils/protein plaques do not exhibit neurodegenerative disease pathology, and 3) amyloid-reducing drugs do not seem to affect neurodegenerative disease progression. It is also true that amyloid is an enticing target for a lot of people with vested interests in this area and those interest may have put too much emphasis on amyloid itself. Like most things in biology though, there is more to the story. Consideration 1: Amyloid itself is a structural characterization of protein assemblies. Amyloid structures generally form in intrinsically disordered (ie unfolded under normal conditions) proteins as a low-energy conformation that is self-templating and derives its stability from a large number of interactions between many copies of the same protein. Amyloid is not really related to protein function in a direct way. The biological roles of disease-associated amyloid-prone proteins (some famous ones are Aβ, Tau, and TDP-43) can be quite varied in the non-amyloid state. These proteins are also associated with neurodegenerative disease through orthogonal means, namely through genetic analysis of disease-related mutations, so it isn't just the fact that these protiens wind up in amyloid fibers that leads us to believe that they're associated with neurodegenerative disease. So, we know because of genetic analysis that these proteins are associated with disease, they can all form amyloid, but we aren't losing any consistent biological function due to their dysregulation–this strongly suggests that the amyloid or otherwise dysregualted state of these proteins is problematic on its own. Consideration 2: Recent structural work has tied different amyloid isoforms to different disease pathologies. I work in an adjacent field to this and these results were really what changed my mind about the validity of the amyloid hypothesis despite years of doubting/discounting it (often in a public way, often to the detriment of my own career–turning the corner on this was a bit challenging). See this paper and the first 5 citations in it (https://www.nature.com/articles/s41586-021-03911-7 https://www.nature.com/articles/s41586-021-03911-7) for a good example of direct structural links between amyloid structure and disease pathology, and the associated comment (https://www.nature.com/articles/d41586-021-02611-6 https://www.nature.com/articles/d41586-021-02611-6) for a good overview. Consideration 3: The presence of amyloid plaques in patients in the real world is generally assessed by histological analysis or other methods that don't capture information at the molecular level. This, combined with the two points above that seem to point to some shared structural features of amyloid-prone proteins being disease causative, suggests to me that studying amyloid (or maybe more specifically the behavior of amyloid-prone proteins) is still a worthwhile endeavor.
• nabla9 4y ago
  Related: Derek Lowe: Had Enough, Eh? Come Back and Take What's Coming to You! https://www.science.org/content/blog-post/had-enough-eh https://www.science.org/content/blog-post/had-enough-eh >It is hard to even begin to estimate the amount of time, effort, and money that has been spent on this idea. And this is just the antibodies! There are plenty of other whacks that have been taken at the amyloid hypothesis (secretase enzymes and more), and none of them have ever worked. Keep in mind that there are plenty of preclinical efforts over the past thirty years that never even saw the light of day (I was on some of those myself), and the reason you never heard about any of them is because they didn't work, either. Nothing has worked. Not once. The amyloid hypothesis has been targeted again and again and again from different directions with different drug candidates, and never, ever even once has it shown signs of truly helping Alzheimer's patients. I very much include Biogen's Aduhelm in that assessment. So I ask again: how long are we going to keep doing this?
• olliej 4y ago
  The amyloid hypothesis is such utter bullshit, at this point there have been empirically effective anti-amyloid plaque drugs. That is drugs that effectively and measurably reduce amyloid plaque build up. None of those drugs have impacted Alzheimers symptoms in any way. If you have a hypothesis of the cause of a disease, and you create drugs that effectively treat it, and those drugs don’t effect the disease symptoms or progression you need to accept the hypothesis is wrong.
  • orangepurple 4y ago
    I have heard people claim that Alzheimers is type 3 diabetes. Is there any truth in that?
    • bpodgursky 4y ago
      Anyone who confidently answers this question is lying.
      • giantg2 4y ago
        I'll confidently answer. We don't know.
        • borodi 4y ago
          So you do know :)
        • fswd 4y ago
          I will take a really risky guess on the premise that there are many different types of causes for Alzheimer's. But one type of them might be caused by parasites. And it's either the body's response or an intended affect of the parasite to enclose the parasite in a type of plague. Kind of like biofilm... or both. Reducing the plague or biofilm could allow the immune system to respond to it by "seeing" it... in some cases. It might also allow the parasite to grow faster if the immune system isn't successful or can't see it. Based on my guess, a treatment plan would involve biofilm/plague "breakers", fasting or behavior changes to reduce and eliminate parasite's life cycle, and anti-parasite medicines that can reach the blood brain barrier. Again, I think there are different types of causes for Alzheimer and this is just one cause.
• anonygler 4y ago
  One might wonder if a similar thing had been happening with low carb / keto diet research. Being adopted as a fad diet has overwhelmed the constant scorn from the nutrition community.
• mturmon 4y ago
  FTA, contradicting the headline (emphasis mine): > Despite being described as a “cabal,” the amyloid camp was neither organized nor nefarious. Those who championed the amyloid hypothesis truly believed it, and thought that focusing money and attention on it rather than competing ideas was the surest way to an effective drug. This discrepancy indicates part of the problem: the investigators narrowing the search for causes honestly believe in what they're doing. The NIH review panelists really believe they're safeguarding the NIH budget, and the Pharma execs really believe they're wisely allocating their R&D budget.
  • jvanderbot 4y ago
    Probably unrelated, but I've realized from dealing with certain people in the criminal justice system, that almost nobody believes they are evil or doing bad things. They just want to do what they think is right, believe that what they are doing is common and acceptable, think often justice takes strange forms, or otherwise can justify what they do till the day they die. The worse someone is, the more strongly they can justify what they do.
    • deleted 4y ago
      [deleted]
    • 300bps 4y ago
      Not unrelated at all. We judge ourselves by our intentions. We judge others by their actions. This leads to people with evil actions judging themselves as good. “I didn’t want to do it. They gave me no choice.”
      • TedDoesntTalk 4y ago
        Do you think Adolf Eichmann saw himself as evil? I do not. He was “following orders” and thereby being good soldier. I would bet Hitler and Stalin also believed themselves to be good people. Same for most all dictators and mass murderers.
        • 4y ago
• moneycantbuy 4y ago
  Plausible alternative causes include herpes virus, diabetes, fungal infection, and/or sleep disorders.
  • smegsicle 4y ago
    also aluminum in some form
    • resoluteteeth 4y ago
      I think that has already been disproven
      • TedDoesntTalk 4y ago
        I have not heard of aluminum being a cause but have heard other toxins such as heavy metals as contributors for certain types of Alzheimer’s (“The End of of Alzheimer’s” by Dr. Bredesen)
        • relaxing 4y ago
          The aluminum hypothesis arose in the late 80s/early 90s.
      • utucuro 4y ago
        Aluminium free deodorant is more expensive where I live, so do you mind pointing to a source or two for that claim?
  • ncmncm 4y ago
    Or bacteria.
• londons_explore 4y ago
  I would bet money that alzheimers will eventually be found to be primarily caused by either a 50+year incubation period transmissible disease or by pollution. As soon as we get good data as to the cause, I think we'll be able to eliminate it pretty quickly. For example if we find that it is spread by contaminated milk, we will make tests for the disease on milk and soon get rid of it.
  • rnk 4y ago
    It's really hard to find causes and later cures for things that come slowly over lives that take many years to hit you.
  • AlbertCory 4y ago
    I'll take that bet. Where do we escrow our money, and who will adjudicate it?
    • ham-sandwich 4y ago
    • DiggyJohnson 4y ago
      I’ll do you a favor and play the bank and the judge ;)
  • SoftTalker 4y ago
    Or maybe it's just one of the ways people die? I'm not convinced that everything has a cause that can be prevented.
• m348e912 4y ago
  "Trust the science" has been a often drummed mantra the past several years but it's important to consider science is subject to bias, group think, influence, and sometimes corruption. (although the latter doesn't seem to apply here) I applaud the researchers who have spoke out against the consensus at their own professional risk, it's a shame they have to take on such burden.
  • sydthrowaway 4y ago
    Now take your logic and apply it to COVID-19.
    • reidjs 4y ago
      Was there a lot of controversy among the scientific community ? The experts seemed to all say pretty much the same thing - masks indoors, social distance, get vaccinated, etc.
      • codefreeordie 4y ago
        Indeed. What would happen to the career of a scientist who even tried to do something else? (many careers were ended. In some cases, states threatened to pull licenses or even imprison researchers for even considering alternatives)
        • nvr219 4y ago
          > states threatened to pull licenses or even imprison researchers for even considering alternatives Where?
          • codefreeordie 4y ago
            All sorts of places, including some unlikely ones. California, Massachusetts, Maine, and Texas all pulled licenses for refusing to uphold the narrative. Washington, Michigan, Minnesota, Illinois, New York, New Jersey, and Arizona all threatened to do so, though I have been unable to determine whether any licenses were actually pulled. California threatened criminal charges, though I have no evidence that any were ever actually filed.
• bryan0 4y ago
  needs a (2019). I'm curious what type of progress in the field has been made since then.
  • jleyank 4y ago
    According to Derek Lowe (in the pipeline), who has written on this at length, none. Other than the fda approving drugs that did not show efficacy that will suck money from Medicare and give families false hope.
  • mandevil 4y ago
    https://www.science.org/content/blog-post/had-enough-eh https://www.science.org/content/blog-post/had-enough-eh Less than a week ago ANOTHER amyloid hypothesis drug failed a Phase III, this from Roche. There are at least three more drugs based on that in Phase III right now (Gantenerumab, Donanemab and Lecanemab). So the drugs that are getting to Phase III are still based on the amyloid hypothesis. Now note that drugs in Phase III are a lagging indicator, so the initial screening and phase 0 research might have changed direction, but the part of the iceberg sticking up out of the water is definitely still amyloid based.
• irthomasthomas 4y ago
  Type 3 diabetes https://en.m.wikipedia.org/wiki/Type_3_diabetes https://en.m.wikipedia.org/wiki/Type_3_diabetes
• jleyank 4y ago
  Pharma has sunk billions into the amyloid hypothesis, fielding multiple candidates to no avail. Good money thrown after bad. Huge market need, has to go back to working out a new animal model. Self-delusion at it’s best, or blind optimism with “this time, it’s going to be different”. Lucy and Charlie Brown snd the bloody football.
• ed 4y ago
  One of the smaller pilot trials mentioned has since posted results (n=33). Valtrex administration over 28 days resulted in a (very?) small improvement to cognitive scores (MMSE in the paper): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919248/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919248/ A larger trial (n=130) is expected to complete by December 2023 (it was originally expected to complete around now, but just finished recruiting): https://beta.clinicaltrials.gov/study/NCT03282916?patient=NCT03282916&locStr=&distance=0&tab=results https://beta.clinicaltrials.gov/study/NCT03282916?patient=NC...
  • ncmncm 4y ago
    I'm taking my valacyclovir periodically, regardless. It might be useless. But it keeps the cold sores down. Got my Tdap, too, because a colossal US Veterans Administration study showed that a recent Tdap booster predicted a 40% reduction in dementia risk. Dunno anything else with that predictive power.
    • derbOac 4y ago
      Acyclovir family meds need to be available over the counter or through a pharmacist. There's actually papers showing that they can be safely taken OTC, and rebuttles basically just saying that "it would set a precedent and increase demand for more meds to be available OTC." To me it's a poster child for the dangers of medication overregulation.
      • MassPikeMike 4y ago
        Topical acyclovir is indeed OTC in Taiwan. A largish tube costs about 7 USD. In the US I needed a prescription for it and that same size tube was a couple of hundred bucks.
        • ncmncm 4y ago
          Topical *cylovir is a weird concept. The virus is inside nerves. Anyway, does acyclovir still work, anywhere?
• codefreeordie 4y ago
  Hmm, I wonder what other high-visibility areas of research suffer from similar problems
  • derbOac 4y ago
    It's all over really. Alzheimer's is sort of an interesting example, but not really fundamentally different in a lot of ways from other areas. Some sure, but some not.
    • codefreeordie 4y ago
      Indeed, really the Alzheimer's situation is unusual only by virtue of being a politically controlled narrative without being partisan. Once you see how corrupt and political something as non-partisan as Alzheimer's research is, you realize how terribly corrupt and purely narrative-controlled "the science" is for partisan topics.
• crawshaw 4y ago
  Committees, like all decision-making entities, are sure to make mistakes. This is a good argument for multiple independent funding sources for research. To some extent these exist, like HHMI. This article does not go into detail about why those institutions did not fund different research, which would be interesting to explore.
• iosystem 4y ago
  My pet hypothesis is that Alzheimer's is the effect of fungi on the body. I think depending upon genetics we have a certain resistance and as we age it weakens. Possibly early onset Alzheimer's could be any factor of exposure levels throughout one's life and or from genetics possibly weakening the resistance of the body towards fungi. While the type of dementia that most elderly develop is possibly the outcome of long-haul exposure to fungi. I've already read some research between fungi and Alzheimer's but not all. I'm just someone who has/had family members with the illness and I'm curious about it. edit: whoever downvotes me, please reply because I'm very curious on if you're downvoting for any specific reason from research that makes you highly doubt my pet hypothesis.
  • forum_ghost 4y ago
    what made you think it's fungi exposure?
    • iosystem 4y ago
      I've been reading research on Alzheimer's from the start of when I became informed about my family members having it. There's multiple approaches that research is going over of course. Some is on fungi like what my comment asserts. If you do a quick google search you can read about it in great detail.
      • TedDoesntTalk 4y ago
        “The End of Alzheimer’s” by Dr Dale Bredesen mentions mold as one vector, but I don’t recall fungi as one. Key insights from that excellent book are that there are several different types of Alzheimer’s, each with a different cause. Other causes have been mentioned in these comments but not all and not comprehensively.
  • WhompingWindows 4y ago
    I didn't downvote you, however I think people may dislike the idea of one having their own pet hypothesis without linking serious evidence to back it up. Amyloid plaques have been heavily studied and may have some tangential but real link to Alzheimer's, it's a plaquey protein found in the brain along with Beta-Tau which is another protein I believe. I personally haven't heard of any fungi theory yet, the main ones I've heard were viral things, pollution, or perhaps some breakdown in the brain's ability to clean itself up over time. And why are certain individuals spared and not others? I know there are genes that predispose one to it, and there are early-onset cases which come on more often than others. If it was anything obvious in the environment, I'd hope we'd know by now...but it may be something hard to measure in large epidemiological studies like a more rare pollutant or something we overlooked in creating large observational datasets? Anyway, I'd encourage you to link the best studies you've found and that may help some to read them.
• redbar0n 4y ago
  Even science is not precluded from dogmatic thinking. Dogmas are everywhere, not merely within religion. In science it’s merely framed as «paradigms». This story details how it looks.
  • dekhn 4y ago
    The fundamental difference is that science explicit recognizes bias and dogma, and works to identify and (to the best of our ability) eliminate its impact on our conclusions. For example- recognition of various biases leads scientists to use randomization and blinding and often scientists have to conclude that they were wrong because the data simply showed their hypothesis was very unlikely.
    • redbar0n 4y ago
      Oh, so science institutionalizes a practise of humility, you mean..? Current article notwithstanding, of course…
      • dekhn 4y ago
        scientists should be humble, but it's not enshrined or institutionalized. The incentive structures took care of that a while ago.
        • redbar0n 4y ago
          yes, apparently it did…
• skissane 4y ago
  Lynn Waterhouse, Eric London and Christopher Gillberg have a similar opinion of autism/ASD: see their 2017 letter to the editors of Autism Research, “The ASD diagnosis has blocked the discovery of valid biological variation in neurodevelopmental social impairment” Some quotes from their letter: > Taken together, the preponderance of evidence argues that using the diagnosis of ASD in research is fruitless because the diagnosis is an arbitrary unscientific “convenient fiction” that has blocked the discovery of replicable neurobiological variation among individuals with serious neurodevelopmental social impairment. > More than seventy years of research studying the arbitrary diagnosis of autism has not resulted in any targeted medical treatments. Now is the time to abandon the ASD diagnosis in research. https://doi.org/10.1002/aur.1832 https://doi.org/10.1002/aur.1832
  • ncmncm 4y ago
    You could say much the same about depression. As it is, we know there are lots of different conditions all labeled depression, distinguishable mainly by which medication they respond to, if any. (This, despite that symptoms vary widely; e.g. many suicidal, others just lacking affect and motivation.) At least treatments exist, somehow grandfathered in. The wastebasket diagnosis means that no new medication can be found to have any useful effect, because it only treats a small fraction of patients in a trial, and worsens others. And, somebody always pops up self-righteously insisting Gold Standard Randomized Controlled Trials prove that none of the medications that millions of people need daily to be able function at all have any effect.
    • R0b0t1 4y ago
      I agree mostly, but w.r.t. medication, it's not that they have no effect, it's that they seem to function by accident with the most plausible explanation (chemical deficiency?) being suspect under closer consideration.
      • ncmncm 4y ago
        No. It is that the med under test could perfectly treat the small number diagnosed who actually have the illness it addresses, and have nil or negative effect on everybody else given the same diagnosis who have an actually different illness. According to the RCT, it just failed. Validity of RCT results is limited absolutely by validity of diagnosis. Bad diagnostics, bad results. That doesn't stop people from running invalid RCTs, so it should stop people from citing invalid RCTs. But it doesn't.
• jyounker 4y ago
  This is why we need more funding for biomedical research. Some proportion of those additional funds need to be distributed on a consistent basis to long-shot or unexplored hypothesis research. The issue is that politicians have for decades described this sort of research as "government waste".
  • derbOac 4y ago
    I think we need a restructuring of the process by which funds are allocated, not necessarily more money (although I'm not opposed to that). My sense is that politicians don't really understand much of the problems affecting research. They hear researchers complain about NIH funding obvious studies, and don't realize that what the researchers mean is "obvious to an expert in any remotely related area", not "obvious to a person with no understanding of the subject matter." Then they pull in experts, and end up with hyper-credentialed persons who have benefited from the very process that needs reform. It's sort of a vicious circle.
• Cupertino95014 4y ago
  > as Aisen put it last week on the sidelines of the Aspen Ideas Festival, “I don’t think I’m part of a cabal.” That's nice. No one thinks they're doing evil. >A frequent reason top journals declined to publish her papers, as they did those of other amyloid skeptics, was previous rejections. As one peer reviewer wrote about a funding proposal Itzhaki submitted in 2010, “very few [of your] papers have appeared in the most highly regarded journals.” I don't think "cabal" is too harsh a word to use here. "Other journals have rejected you, so we will, too." > One of the four reviewers gave her scores of “poor” (3 on a 10-point scale) on key criteria, arguing that because “there is no conclusive evidence for a major role of this pathogen in Alzheimer’s disease,” the research “will not have an impact on advancing the field of dementia research.” A second reviewer called the role of pathogens in Alzheimer’s “a fringe topic.” Although one gave Itzhaki scores of 10 (“outstanding”), the two dismissive reviews sank her chances. If the amyloid hypothesis had made stunning progress, that approach might have made sense. If not... "the jury is still out, so let's hear your ideas" would be the real Science.
  • deleted 4y ago
    [deleted]
  • bombcar 4y ago
    Surprisingly large amounts of people are lazy, and copying whatever was done before and changing up the words a bit covers most everything most of the time.
    • AlbertCory 4y ago
      Yep. I've been lucky enough to work with a few people who are (mostly) open to hearing evidence they don't agree with. It forces you to up your game, for sure. It's always harder to convince them than when they already agree, but at least it's not impossible.
      • bombcar 4y ago
        To be fair, I can’t imagine having to explain to students why their perpetual motion machine won’t work year after year.
• dang 4y ago
  Related: (are there others?) Alzheimer’s amyloid hypothesis ‘cabal’ thwarted progress toward a cure (2019) - https://news.ycombinator.com/item?id=31828509 https://news.ycombinator.com/item?id=31828509 - June 2022 (307 comments) How an Alzheimer’s ‘cabal’ thwarted progress toward a cure - https://news.ycombinator.com/item?id=21911225 https://news.ycombinator.com/item?id=21911225 - Dec 2019 (382 comments) The amyloid hypothesis on trial - https://news.ycombinator.com/item?id=17618027 https://news.ycombinator.com/item?id=17618027 - July 2018 (43 comments) Is the Alzheimer's “Amyloid Hypothesis” Wrong? (2017) - https://news.ycombinator.com/item?id=17444214 https://news.ycombinator.com/item?id=17444214 - July 2018 (109 comments)
• jnovek 4y ago
  "This stifling of competing ideas, say a growing number of scholars, is a big reason why there is no treatment for Alzheimer’s." Question for those who know: is this a problem in general with the culture of academic science? I am not a scientist, but I feel like I've seen this story more than once in science-enthusiast media: an established but incorrect idea cannot be challenged because it is a risky career move and hard to get funding for. I understand that crackpots exist, but I wonder how much of this culture is really a barrier to keep out the unsubstantiated and how much of it is just protecting turf and sunk costs? I have tons of confidence in the scientific method, but decreasing confidence in the institutions that practice it.
  • Obi_Juan_Kenobi 4y ago
    The idea of an oppressive scientific elite is a bit too neat and tidy. Certainly there are banal human politics at play, but it's hardly an explanation for all that ails. This idea is too attractive to the heterodox and outsiders cynical of scientific institutions. Alzheimer's research having a focus on amyloid plaques makes perfect sense in light of so much data implicating it as a mediator of the disease. It's hard to say, even in retrospect, whether this focus was warranted or not. Allocation of scarce resources is hard, and everything comes at the expense of something else. It's easy to pick out 'fringe' ideas that bore fruit and lament how hard it was for them to gain traction. But what about all those that didn't? Were we really balanced too strongly to dominant ideas, or is science simply difficult? You simply can't address this issue with the recent success of new or fringe ideas. You'd have to do something like systematically look at proposal acceptance rate vs. some subjective measure of heterodoxy vs. ultimate success. I just don't see compelling results from something like that.
  • ncmncm 4y ago
    Yes, it is a problem in general. It is inherent in the system that issues grant money and permits publication according to the opinions of the "old guard" in each field. Recently, the Younger Dryas Impact Hypothesis, finally firmly established in 2018, was fought tooth and nail for a decade, with numerous shamefully disingenuous papers published (e.g. insisting melt-glass grains were pollen). The de-facto curator of the Wikipedia page, a retired historian with no geology background, did and still to this day does his part to throw up doubt.
• pessimizer 4y ago
  > For young academics, biotech executive Dr. Raymond Tesi said, "it’s difficult to break into a field with so many strong voices supporting a single target. Alzheimer’s has egos and superstars and big personas unlike anything I’ve seen elsewhere." For a field with no real results to have "superstars" is a sign of corruption.
• aamargulies 4y ago
  This reminds me a bit of the role string theory plays in the physics community.
  • ncmncm 4y ago
    Some say that string theory gets much of its pull from physics departments who favor string theorists as faculty who do not need and will not provoke lab work.
• philsawa 4y ago
  https://usrtk.org/sweeteners/aspartame_health_risks/ https://usrtk.org/sweeteners/aspartame_health_risks/ This article links Aspartame to some wild problems. One of them is Alzheimer's. In the early 2000s i worked for a pharma company. A woman named Beryl told me they knew aspartame caused Alzheimer's if it went over a certain temperature.
• seydor 4y ago
  This is old, does not include Biogen's drug.
  • amluto 4y ago
    You mean the one that doesn’t work? The article points out the trial was stopped because the drug did not work. The only thing that changed is that the FDA approved it anyway. All available evidence still suggests that it doesn’t work.
    • seydor 4y ago
      The evidence is inconclusive not negative. That trial was halted but later restarted. There is some evidence that it works, and this is better than any other potential treatment which has not shown any evidence. And alzheimers is a fatal disease
      • amluto 4y ago
        Aduhelm is also a potentially fatal drug. Even ignoring cost, evidence that the tiny amount of good that it might do exceeds the clearly evident harm it can do is, to put it mildly, lacking. https://www.reuters.com/business/healthcare-pharmaceuticals/biogen-probes-death-aduhelm-user-after-brain-swelling-2021-11-09/ https://www.reuters.com/business/healthcare-pharmaceuticals/... Keep in mind that, while only one patient was known to have died at the time the article was written, not a whole lot of patients had been treated.
• ncmncm 4y ago
  The only really promising treatment effect I have seen in recent years was in a huge, broad study of Veterans Administration patients (N tens of thousands) conducted over a 6-year data set. What they found was that having had a Tdap vaccination booster recently predicted a 40% reduction in dementia risk. They then replicated the result with a wholly disjoint population treated in a different system. 40% effect is better than aspirin for headaches. A confounding factor with that much correlation would be almost equally interesting even without causative effect. I don't know of anything else that predicts dementia risk. They had no idea which component of the Tdap vaccine might be responsible. But you can bet I went out and got my Tdap booster right away. Because why not?
  • cogman10 4y ago
    You see these sort of correlations a lot and I have to wonder, is this a wealth predictor? That is, is it that someone who is more likely to get their TDAP is also likely has a more stable life. You see these sorts of things a lot in health studies. For example, someone that goes to church often is more likely to live longer. Yet, if you look at what's happening, someone that isn't going to church is more likely doing that because they can't (IE, they are bed ridden) which in and of itself is a strong predictor for whether or not you are going to die soon. Disentangling these sorts of cause and effects seems like something medical journalism does poorly.
    • ncmncm 4y ago
      That kind of confounding is something that it is well understood how to filter for, by matching cohorts. It is possible when N is in the tens of thousands. But their report did not say the effect was more pronounced in any particular selection of cohorts, other than as noted.
• IanDrake 4y ago
• georgewfraser 4y ago
  There is no better way to get shut out as a scientist than to disprove the career-making findings of the important people in your field. One of the side effects of this is the “discussion does not match the results” paper. It’s routine to read papers where the discussion blatantly contradicts the papers own results. What is happening is the authors are disclaiming their own findings in order to get past hostile reviewers, betting that astute readers will notice the contradiction, ignore the discussion and draw their own conclusions from the results.
• DoreenMichele 4y ago
  This stifling of competing ideas, say a growing number of scholars, is a big reason why there is no treatment for Alzheimer’s. (The four approved drugs have no effect on the disease, providing only a temporary memory boost.) Those who championed the amyloid hypothesis truly believed it, and thought that focusing money and attention on it rather than competing ideas was the surest way to an effective drug. Or maybe the real problem is the excess emphasis on finding a drug in specific that can be commercially monetized. A single drug for a single cause of what is likely a complex process. Amyloid and another protein (tau) accumulate in the brain due to sleep deprivation. Helping people get a good night's sleep -- without drugs -- would likely help, if only to stave it off in those at risk. The problem is it won't create any razzle dazzle "unicorn" companies and newly-minted zillionaires. One of the researchers in the article found that herpes simplex infection promotes the accumulation of amyloid. Her research was not irrelevant to the amyloid hypothesis. It was only irrelevant to an agenda to find a drug to treat amyloid.
  • wins32767 4y ago
    Drugs that can't be commercially monetized can't get through the rigorous and extremely expensive approval process that allows your doctor to write you a script for something you can fill at the pharmacy. As for other treatments, medicine basically boils down to surgery, drugs, and/or letting your body heal itself. The latter clearly doesn't work and for progressive diseases surgery generally isn't effective, so you're back to drugs.
    • ClumsyPilot 4y ago
      Thats not true. Many conditions are well adressed by informing and training those at risk how to best take care of themselves. Current medicide really fails at this. In fact it fails in many arreas where a longterm and consistent influence is required. Getting diagnosis and treatment for vitamin defficiency, hormonal imbalance, stomach microbiome, psycology related issues, and many other conditions simply does not happen unless patient does his own reading and pesters the doctor for treatment.
      • 4y ago
• m463 4y ago
  I've read that sildenafil (viagra) might decrease the disk of alzheimers (or correlates with a lower risk of alzheimers) https://pubmed.ncbi.nlm.nih.gov/32467879/ https://pubmed.ncbi.nlm.nih.gov/32467879/ https://pubmed.ncbi.nlm.nih.gov/32959702/ https://pubmed.ncbi.nlm.nih.gov/32959702/ also, sleep deprivation increases the alzheimer's protein: https://www.nih.gov/news-events/nih-research-matters/sleep-deprivation-increases-alzheimers-protein https://www.nih.gov/news-events/nih-research-matters/sleep-d...
• wesleywt 4y ago
  Normal. Science is not perfect. It proceeds one PI death at a time.
• narrator 4y ago
  There's always methylene blue under development by TauRX and in stage 3 trials. https://taurx.com/the-science/clinical-trials https://taurx.com/the-science/clinical-trials. Even more amusing is that you can take methylene blue right now as Troscriptions sells a non-prescription product containing pharmaceutical-grade methylene blue intended by the manufacturer for human use. Yes, your tongue will turn bright blue.
• rob_c 4y ago
  Biomed in a nutshell unfortunately, especially where there are research costs to be burdened. There are more stories like this that will come out eventually over time. Unfortunately you're branded another Alex Jones for saying this out loud.
• projektfu 4y ago
  I think we're seeing a similar thing shake out with atopic dermatitis, long thought to be related to type 1 hypersensitivity but not treated by antihistamines and poorly treated by steroids. The development of JAK inhibitors has created a new industry in treating many types of immune mediated disease and I have not seen the immunology texts rewritten yet.
  • benrapscallion 4y ago
    The development of JAK inhibitors for dermatology was not limited by any hypothesis but because of the multifaceted risk conferred by JAK inhibitors including increased risk of cancers.
• hitovst 4y ago
  "Healing Our World" by Dr. Mary Ruwart
• rdl 4y ago
  The real problem is the cost of discovering/developing drugs. If this were vastly cheaper we could do more faster.
  • DiggyJohnson 4y ago
    How is this actionable?
    • rdl 4y ago
      Various ways to reduce trials costs. Refocus FDA on safety vs efficacy. Computer simulations.
• subroutine 4y ago
  AD researcher here (late to the thread). As much as I loath the 'cabal' mentality, I personally think amyloid-beta is the cause of AD. Just because a few treatments focused on Abeta haven't cured AD isn't convincing in the slightest that Abeta accumulation is not a causative mechanism. (1) AD is a disease of the elderly - a group not particularly receptive to treatment, (2) AD pathology is likely due to a sequelae that took decades to manifest into symptoms; undoing tens of years of buildup is not going to be easy, (3) even if the treatment could clean up a large portion of Abeta accumulation (and that's a big IF) it wont restore lost memories. With regard to evidence, the article mentions APP gene variant causes early onset AD; but there is another variant in the APOE gene that is the strongest genetic risk factor in late-onset AD. This gene too is in the Abeta buildup pathway. With that said, I think that NIH study sections allocating AD research funding should not give preference to a particular molecule or theory. If the Abeta hypothesis is indeed the most compelling, grants focused on Abeta topics should naturally be stronger. They shouldn't need any additional bias to stand out.
  • throwawaymaths 4y ago
    ApoE is not necessarily in the a-beta buildup pathway. One idea that was tossed around was that increased cholesterol yielded alkylation factors (like 9Hydroxy nonenal or oxidized cholesterol metabolites) that then modify a-beta but there's not really any strong evidence that that happens in vivo. Iirc there's something about lipid raft homeostasis being out of whack leading to increased likelihood of amyloid nucleation, but our ability to measure lipid rafts in vivo is even weaker.
  • nabla9 4y ago
    There is plenty of evidence against amyloid-beta hypothesis. (1) Pathological levels of amyloid-beta and tau are present in cognitively normal individuals. (2) Some individuals clinically diagnosed with AD do not have amyloid-beta pathology (3) spatial appearance, progression and absolute amount of amyloid plaques does not correlate with declining cognition more conclusively than other pathologies. (4) It's not even clear that that amyloid-beta pathology is the first AD biomarker. Not even among those with APP, PSEN1 and PSEN2 biomarkers. (5) it looks like autosomal dominant AD may be a different disease than sporadic AD and results there don't apply.
• praptak 4y ago
  I don't believe there is more to it than the researchers getting exploration/exploitation wrong in this case. Say somebody wants to get funding to fight AIDS, based on the hypothesis that it is caused by something else than a virus. The research community would oppose funding this and they would be right. At some point you have to reject some hypotheses, there's just not enough time and researchers to keep researching every not-so-promising hypothesis. Sometimes the research community will get that wrong but this is the cost of having research focused on the most promising hypotheses.
• smsm42 4y ago
  Is there a chance we take it as a teachable moment and ask ourselves if there are other areas where we feel OK to suppress alternative approaches and ideas, and where we're going to pay dearly for it later?
• miq333l 4y ago
  what I wonder, is, what other cartels of this type stifle progress in science..
  • DiggyJohnson 4y ago
    Yes. What is more significant is the magnitude of the problem itself. Consider String Theory.
• joelthelion 4y ago
  As much as this is a good story, I don't think the Amyloid hypothesis has been disproven yet. We have several very large phase 3 studies in the pipe, with results expected in the next few years. If they all fail, it will be pretty clear. But we're not there yet.
• tpoacher 4y ago
  I think the "cabal" hypothesis is stretching it too much (especially where a malicious element is implied). But the whole "at least spinkle some [latest trending buzzword] in your proposal otherwise you won't get published/funding", is absolutely 100% true. Anecdotally, I wrote a paper a few years back, which solved a problem with fuzzy methods. Fuzzy methods are considered "obsolete and superseded by Bayesian methods" by many, which mathematically is borderline retarded, since fuzzy measure theory is in fact a superset of probability theory. My then supervisor urged me to include a whole paragraph on how "these methods we're proposing are some new kind of fuzzy that draws from bayesian mindsets and any relationship with traditional fuzzy methods is purely coincidental for lack of a better name bla bla bla ..."
• pimpampum 4y ago
  Scientists are pretty fanatic about their paradigms for people of science...
• crikeyjoe 4y ago
  Let's get back to science.
• pedalpete 4y ago
  I have a dog in this fight as the founder of neurotech/sleeptech start-up https://soundmind.co https://soundmind.co, however we are NOT looking at an Alzheimer's treatment, but rather prevention. I'll pick up on the thread of "telling people to get better sleep" is insufficient. Amyloid plaques are cleared through the glymphatic system, and the clearing coincides with slow-wave oscillations (SWOs). It is believed that the SWOs trigger the clearing, and this is a current area of research with a group we are connected to. Your sleep naturally degrades as you age, and, in particular, we get less of these very important SWOs. Auditory stimulation has been proven to increase the power of SWOs and there is lots of research on the related cognitive improvements seen after just one night of stimulation. There are also hormonal responses related to the immune system, and many other benefits. A cure for Alzheimer's is important, but improving the neurological function of sleep, what we call Sleep Performance, is more important. It's like the difference between telling somebody to eat a good diet, or get more exercise rather than coming up with a pill they can take when they are already obese. If you want to find out more about the science behind the SoundMind DeepWave stimulation, check out https://soundmind.co/research https://soundmind.co/research - there are more papers I will be adding to that page shortly.