14 ms·

Why I’m Digging Deep Into Alzheimer’s

• melling 9y ago
  His first donation is $50 million to this private organization: http://theddfund.com http://theddfund.com
• reasonattlm 9y ago
  The slow pace of progress towards clearance of amyloid, in that only in the past year has one of the immunotherapy trials actually looked promising, has provoked a lot of alternative theorizing these past five years. Some it is clearly not so great, such as the fellow who argues that it is caused by rising use of paracetamol (see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921468/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921468/ ), but some lines of theory are much more compelling. A more encompassing synthesis is emerging in which microbial infection by spirochetes and gum disease bacteria (e.g. see https://doi.org/10.3389/fnagi.2017.00336 https://doi.org/10.3389/fnagi.2017.00336 ) that can provoke amyloid formation as well as failing drainage of cerebrospinal fluid (e.g. see https://doi.org/10.1002/ana.24271 https://doi.org/10.1002/ana.24271, https://www.ethz.ch/en/news-and-events/eth-news/news/2017/11/exit-through-the-lymphatic-system.html https://www.ethz.ch/en/news-and-events/eth-news/news/2017/11..., etc) that stops removal of amyloid, tau, etc are as important as purely cell focused considerations of the biochemistry of amyloid beta. For an example of the new type of venture emerging now as a result of all of this you might look at Leucadia Therapeutics, working on a way to restore drainage through the cribiform plate, but there will be more in the years ahead to complement the immunotherapy for amyloid and tau mainstream.
  • Mr30 9y ago
    >> A more encompassing synthesis is emerging in which microbial infection by spirochetes and gum disease bacteria Wow, I did "notice" a strong correlation between gum disease and dementia in my own Family. This is obviously my own uneducated guess but it's humbling to see serious people looking into it! There very well could be some sort of dementia that is indeed related to gum disease!
    • redcalx 9y ago
      I believe gum disease is also correlated with cardiovascular disease.
• yhvh 9y ago
  https://www.brainwavebank.com/ https://www.brainwavebank.com/
• maxst 9y ago
  >Most of the major pharmaceutical companies continue to pursue the amyloid and tau pathways. Dementia Discovery Fund complements their work by supporting startups as they explore less mainstream approaches to treating dementia. That's very encouraging. Because what if it's something else?
  • Filligree 9y ago
    The amyloid and tau pathways are our best hope of finding a simple solution, something we can reasonably fix with drugs. If it's something else, then chances are good it'll be far harder to fix, perhaps even requiring genetic engineering or medical nanotechnology. Finding out is still valuable, of course...
    • hprotagonist 9y ago
      We’re batting 000 on drugs that target amyloid or tau, and not for want of trying.
      • Filligree 9y ago
        Fortunately, we have enough resources to try multiple approaches. I'm happy that we're doing so. For a very long time this was treated as just a fact of life, immutable.
    • gerbilly 9y ago
      > our best hope of finding a simple solution You hit the nail on the head, and I think you bring up an interesting point. Ask anyone who has a condition stigmatized by the medical community, say chronic fatigue, about how the medical system reacts to their symptoms. You will find that in a many cases, doctors will try to deny the existence of the disease. I think this is because it is so complicated as to elude a 'simple solution'. Perhaps our doctors and medical researchers, are too predisposed to look for simple solutions in these cases, because that approach worked so well in the past. Maybe we've picked all the low hanging fruit, and now it's time to tackle the tougher problems, using a more system-wide approach. We seem to be stuck in the mindset of: single disease/single cause/single solution.
• _Marak_ 9y ago
  It's interesting to note that tetrahydrocannabinol and other compounds found in marijuana may reduce the amount of beta amyloid in the brain. Beta amyloid is commonly thought to cause Alzheimer's disease. see: https://www.nature.com/articles/npjamd201612 https://www.nature.com/articles/npjamd201612 Last I heard in the US, the Federal government was still making it difficult to run clinical trials for Alzheimer's using marijuana. I think any federally funded medical trial using marijuana needs to be approved by the DEA.
  • Beltiras 9y ago
    It's more complex than just that. At CTAD just a couple of weeks ago there was a presentation on drugs that managed to reduce AB (biomarker was inferred by a PET scan) and it did not result in increased cognition.
    • SirensOfTitan 9y ago
      Could it be that the presence of beta amyloids already caused structural changes to the brain? I know nothing about Alzheimer's.
    • eganist 9y ago
      A simple hypothesis which could explain this might be that the plaques cause effectivelt permanent brain damage. The question is whether degenerative patterns ceased or slowed after substantial clearing of plaques from the brain. I would expect this test (and therefore the hypothesis) to fail if the plaques themselves are a byproduct rather than the cause of degradation in brain function. That said, I'm surprised I haven't read much in Gates' Notes or other funding sources on potential ties to HSV1 considering all the increasingly supportive research between the two.
      • JamesBarney 9y ago
        They used several techniques that clear beta amyloid from the brain.(antibodies and ultrasound). And they've have little if any effect on cognition. I'm starting to think beta amyloid is a red herring, or maybe just important in the prodromal stages of the disease.
• ggambetta 9y ago
  Cynical answer: "because I'm getting old" :) Whatever the reason, this has the potential of being life-changing for a lot of people. Would love to see more billionaires involved with this kind of initiative.
  • melling 9y ago
    Would love to see more non-billionaires involved. You might not be far off on “he’s getting older”. When you’re younger, you don’t think about the impact of “old people” diseases. Hearing that a couple billion people will get Alzheimer’s is not nearly as impactful as seeing someone a little older than you with it.
    • ido 9y ago
      Don't know about you but seeing my grandparents getting senile was enough to get me thinking (and fearing) "old people problems".
  • Filligree 9y ago
    The reason doesn't really matter, this is still incredibly valuable work. Death is terrible, and should be eradicated, but Alzheimer's is a few steps above that. There's nothing worse than seeing a loved one be slowly destroyed by that horrific disease, and I'm so glad there are people willing to work on it.
    • pmelendez 9y ago
      "Death is terrible, and should be eradicated" We are sensitive to death but it is the only mechanism I know that would control overconsumption of natural resources. If nobody dies, then we would deplete the resources in a few decades.
      • sheepdestroyer 9y ago
        We have death and at the same time over-consumption, so the control is not working that well. Did you mean that it would effectively control the over-consumption if better implemented (with a higher rate)?
• vasco 9y ago
  Disable the shitty auto-pausing of youtube video on scroll by pasting this on the console: getEventListeners(document.getElementById('tgnbody')).scroll.forEach(function(el){document.getElementById('tgnbody').removeEventListener("scroll", el.listener)})
  • tzahola 9y ago
    Thanks! I'd love to have a browser extension which automatically augments shitty websites with community-sourced javascript snippets. E.g. you'd visit idk Forbes.com, and saw that the site is unusable b/c of some shitty undismissable paywall overlay. You "fix" the issue with a few lines of JS, and then upload it via the extension. After going through some kind of vetting/review, the extension will automatically fetch and run your JS fix for everyone who visits the site.
    • andygates 9y ago
      Wasn't Edge supposed to support shareable annotations? That's nearly code...
    • robbyt 9y ago
      Grease Monkey?
      • tzahola 9y ago
        Does GreaseMonkey suggests you scripts based on the current site you're visiting?
    • jmkni 9y ago
      I'm using Just Read on Chrome, if you're on a shitty website hit the Just Read button and it pulls out the text, works pretty well.
  • smoyer 9y ago
    I didn't know there was a youtube video because (apparently) a key component of this site was blocked by Ghostery and/or uBlock. Message to most websites that fail to load without their cruft - I just don't need you.
• bflesch 9y ago
  It's great to see more investment into this disease. When my grandma fought Alzheimer's over the span of a decade it was very striking to see that the effect of a lack of hydration and the disease itself kind of overlapped. When she had a particularly bad day we used to give her a saline IV and you could immediately notice how she cleared up and regained her brain powers after each IV. I'm not up to date on current research into that direction, but I think hydration plays a very big role in Alzeimer's symptoms on the elderly. I know it sounds ridiculous, but once I'm rich enough I want to build an elderly care center/hospital with urine-based hydration monitoring for each participant so family members can be sure that their loved ones have a healthy water intake each and every day.
  • taf2 9y ago
    I think the toilet in general could use an upgrade... for how many years have they been built exactly the same way? Has anyone ever done a study of the flow as urine impacts the toilet and bounces back? Or as we learn more about the importance of stomach bacteria, can our toilet start to do more monitoring of the bacteria in our stomach? Love your idea of hydration monitoring and think the application is probably more far reaching than just Alzheimer’s
    • bflesch 9y ago
      Yes, I think it makes more sense to monitor and gather data on what comes out of your body instead of monitoring what goes into it(e.g. all smartwatches/diets). I'd like to one day have a room-sized analysis unit which screens feces/urine of all attached toilets and performs various tests on it. Analysis results could be assigned to individuals based on the DNA footprint. It could immediately tell you that your sugar intake is too high or that you should drink more water. With this kind of immediate feedback people will be able to live healthier because they can correlate food <-> result on their body. Also we could do so many interesting studies..
      • StudentStuff 9y ago
        It'd be great to be able to pull glucose, hydration and more out of urine samples real time, so long as we stay away from say live telemetry to insurers or something like SmartPipe[1] it'd be enormously beneficial. 1 - https://www.youtube.com/watch?v=DJklHwoYgBQ https://www.youtube.com/watch?v=DJklHwoYgBQ
• madshiva 9y ago
  no need to have Alzheimer to see these poor old guy / women that can't do anything. We should die sooner, waste less resource and enjoy more.
  • Chris2048 9y ago
    What would you suggest?
    • madshiva 9y ago
      Don't extend life...we discovered these things because we are older and older. I don't think that the solution is getting older. Don't know why I'm always getting down vote too. Life and his mystery.
      • Chris2048 9y ago
        What about the elderly people who don't have problems?
  • Angostura 9y ago
    There are some people would would like to die. There are many who get true enjoyment from life well into their 90s.
  • zionic 9y ago
    I've never understood this degenerate self-loathing that exists within the environmental scene. It's completely toxic to the green movement.
  • sctb 9y ago
    You've been posting a lot of uncivil and unsubstantive comments. Could you please take a look at the guidelines and start following them? https://news.ycombinator.com/newsguidelines.html https://news.ycombinator.com/newsguidelines.html
• arghwhat 9y ago
  Heh, the blog fails to load in Firefox 57...
  • Jhsto 9y ago
    Same thing (the text does not appear) happens if you have Ghostery on blocking all the trackers.
    • aorth 9y ago
      I'm running Chrome + uBlock Origin here and text does not appear either. Same in Firefox 57 + uBlock Origin, although reader view shows the text.
    • bahjoite 9y ago
      Same. And with nearly thirteen thousand lines in the source of the page you'd think the text would be there too. edit: oh, there it is, 25 lines beginning at line 8201.
      • noir_lord 9y ago
        > oh, there it is, 25 lines beginning at line 8201. This comment made me laugh with the tragedy that is the modern web.
    • jmkni 9y ago
      Ditto on Chrome
  • louhike 9y ago
    I do not have any problem on it with Firefox 57. Are you sure it's not because of an extension ?
  • Tharkun 9y ago
    Switch firefox to reader mode (the book icon in the address bar), that seems to fix it.
• Beltiras 9y ago
  I work for a company[1] in this space. We make software that analyses EEG recordings and predicts if the subject will develop Alzheimer's. We are currently working on Class 2 CE mark for our AD product. [1]: http://www.mentiscura.com/ http://www.mentiscura.com/
  • docere 9y ago
    Is this promising tech? EEG may be sensitive but not very specific.
    • Beltiras 9y ago
      Wouldn't be working on it if it weren't. I can't go into specifics.
• bitL 9y ago
  FYI, taking sauna 4x a week seems to lower the risk of developing Alzheimer significantly (at least in Finland). I can also observe myself that taking hot phase 4-5x for 10-15 minutes followed by 2 minutes cold immersion every time in roughly 1.5 hours clears my brain/senses. Maybe the sweating helps overloaded brain drainage as well? I think Bezos must be applying some of these hacks on himself; he got recently in shape while in previous decades he seemed to let himself go. Bill might think about the same as he is visibly deteriorating and his liver seems to be not functioning well (spots on his skin everywhere). They should add calorie restriction/frequent fasting as well. It's unlikely they will beat the death, but might make their final moments less horrible.
  • bshimmin 9y ago
    Bill might think about the same as he is visibly deteriorating and his liver seems to be not functioning well (spots on his skin everywhere) I think he's always had freckles, no?
    • bitL 9y ago
      If you see some recent unedited footage of him speaking, it got much worse. I personally know one soon-to-be-a-billionaire that is heavily funding his own biotech/longevity research to buy more time, yet is hopelessly out of shape and doesn't have the same discipline on his own body he has for his companies. It's paradoxical when you think about it, kinda broken feedback loop.
  • tallanvor 9y ago
    Liver spots are the result of aging sun exposure. A long time ago they were thought to indicate an issue with the liver, but there is no connection between the two. They are not at all an indicator of health. The only affect they have medically is that they can make it harder to detect skin cancer when doing a visual exam.
    • bitL 9y ago
      Thanks, I'll update my knowledge :)
• yitchelle 9y ago
  Just relistening through some of RadioLab's podcast. I came across this apt episode about Gamma Light Therapy. Adding it to the mix. When I listen to this episode, I had a hint of hope for my dad who is suffering dementia in the past few years. http://www.radiolab.org/story/bringing-gamma-back/ http://www.radiolab.org/story/bringing-gamma-back/
  • new299 9y ago
    It seemed like such a simple treatment, that it should be relatively easy to test more widely... But whenever I've searched, I've not seen an update. For those who haven't listened to the podcast, the treatment is effectively just being exposed to a 40Hz (IIRC) flashing light. Which sounds surprisingly simple.
• gk1 9y ago
  Even younger people can be afflicted with Alzheimer's (called Early-onset Alzheimer's), and it's even more terrible to witness. It's one thing to watch a human mentally deteriorate when they are at the end of their life, it's another thing to watch it happen to someone in their 40's—who should be in the prime of their life and raising their children.
  • autonomy77 9y ago
    >>It's one thing to watch a human mentally deteriorate when they are at the end of their life<< Alzheimers is terrible to witness at any age - the elderly included. While it's certainly tragic to see in younger people, it's no less tragic to see older people in a state of fear and panic, when they should be enjoying their twilight years.
  • yeukhon 9y ago
    Yes. The thing is once you are an Alzheimer's patient, you are doomed because your brain basically stop being able to function at the very end. It's like a death kiss from the above. Unlike cancer, which is scary as hell, and has a high death rate, has better chance of surviving. The pressure on Alzheimer's patient and on the family is just unbearable. While there are some treatments to slow down the progress, we are far from understanding the disease itself, let alone knows how to combat the plaque and tangles effectively. Right now I think one of the best treatments is let patients be more active, whether it's playing chess or gardening, while receiving family support. The more positive we are the better we are overall health wise. This is evident in patients who suffered depression.
• raleec 9y ago
  I remember that ultrasound[0] was very promising a few years back. Does anyone have any more recent info? [0]: http://www.sciencealert.com/new-alzheimer-s-treatment-fully-restores-memory-function http://www.sciencealert.com/new-alzheimer-s-treatment-fully-...
• xkcd-sucks 9y ago
  Finally, a cause that can eat up the entire Gates fortune without breaking a sweat
• louprado 9y ago
  The documentary "Under our Skin" details Alan MacDonald's breakthrough research on how Lyme disease causes Alzheimers. The 4 minute trailer is worth a watch[1], but basically Lyme disease is found in 7 or 10 brains of Alzheimers patients (small sample set). The Lyme disease spirochete literally drills countless pathways in the brain and that causes slow dementia. That spirochete also creates a biofilm which makes it challenging to detect in a living patient. His research is from a decade or two ago. Also I wonder how a citizen scientist like Gates does a deep dive on this topic a like this. There are 10's of thousands of research papers on the subject[1] and countless books. [1] https://www.youtube.com/watch?v=GCLwauRh2gQ https://www.youtube.com/watch?v=GCLwauRh2gQ [2] http://archive.sciencewatch.com/ana/st/alz2/journals/ http://archive.sciencewatch.com/ana/st/alz2/journals/
  • joewee 9y ago
    Re Gates; he and his staff identify Subject Matter Experts (SME) for the topics he’s interested in. As you can imagine he has a good network. SMEs are always looking for funding, so he’ll use one of his funding vehicles to invite the SME to apply for funding or meet with the organization. By the time you meet with Bill Gates he would have read your most recent papers and competing theories and will be prepared to challenge you on your approach. Pass his final intellectual test and you are added to his collection of SMEs. <source: me, I’ve seen the process> Edit: When I had the pleasure of watching Bill Gates do this, it was one of the most impactful moments in my life. When he would question a SME on a topic he came across as knowledgeable as the SME who has dedicated years to the topic. Bill Gates literally will have read all around the topic and his mind operates like a poker player or chess player who is thinking on multiple levels. His questions are probes to see how many levels you are thinking on, and I think it also informs him of other angles. He’s a brilliant guy.
    • skybrian 9y ago
      SME seems be "subject matter expert".
      • pouetpouet 9y ago
• judah 9y ago
  Michael Fossel and his biopharmaceutical company Telocyte claim[0] to have a novel, effective treatment for Alzheimers, one that does not simply target the amyloid and tau pathways. Telocyte's treatment is based on telomerase gene therapy, and is currently undergoing FDA safety trials. According to Fossel, their telomerase gene therapy reverses cognitive decline in animal models, and they're confident the same will apply to humans. Human trials begin in 2018. I wonder whether Gates has seen Telocyte's work. [0]: http://www.michaelfossel.com/blog/?p=249 http://www.michaelfossel.com/blog/?p=249
• rikelmens 9y ago
  Prevention, prevention, prevention.
• leekyle333 9y ago
  The Buck Institute has been doing a lot of great research on alzheimers. They are taking a very different approach though. Tinkering with everything from diet, to infections, to heavy metals, to hormone optimization. Here is a good podcast with one of the main researchers from the Buck Institute. https://www.youtube.com/watch?v=HS7VZydS8HI https://www.youtube.com/watch?v=HS7VZydS8HI It's crazy how much focus has been on clearing amyloid without much luck at all. 224 clinical trials and only 2 drugs going through.
• dawhizkid 9y ago
  I believe there are already studies out there that link excess sugar intake with increased risk of Alzheimer's? I think this is yet another case for a ketogenic diet/intermittent fasting...
• jwilk 9y ago
  Archived copy, which can be read with JS disabled: https://archive.is/rDJ6G https://archive.is/rDJ6G
• Nomentatus 9y ago
  Funny, I remember contacting the Gates foundation many years ago now about chronic illnesses and the then-new discovery of ipRGCs/pRGCs (which we will find have a critical role in Alzheimer's) and hitting a total brick wall. Paraphrasing them, "this wouldn't help the third world" - we know better now.
  • stdgy 9y ago
    Bill addresses this in the piece: I’m making this investment on my own, not through the foundation. The first Alzheimer’s treatments might not come to fruition for another decade or more, and they will be very expensive at first. Once that day comes, our foundation might look at how we can expand access in poor countries. It's intriguing they're able to draw that line, but it makes sense if they want to keep the Gates Foundation focused.
    • Nomentatus 9y ago
      But note that obesity and diabetes (Alzheimer's is sometimes called diabetes 3 and called part of the metabolic syndrome) are now hitting the third world HARD. Something that was highly predictable, and which I feared and mentioned at the time.
      • allenz 9y ago
        The Gates foundation allocates funds based on dollars per Daly (disability-adjusted year) impact. Alzheimer's is important research but it doesn't meet that criterion. Unlike metabolic syndrome (under the traditional definition), Alzheimer's is overwhelmingly late-onset, and the research is also riskier and more expensive.
        • Nomentatus 9y ago
          You jest. Grab some of the estimates of just how staggering the costs will be to us of Alzheimer's alone; as for the third world chronic illness (obesity, diabetes) is already beginning to crush their nascent medical systems. As clearly stated above I contacted them re chronic illness as a whole, not Alzheimer's specifically.
• nikolay 9y ago
  The new research [0] on similar causes of diabetes, Alzheimer's, and cancer is exciting as one could target major killers at once. [0]: https://www.youtube.com/watch?v=KSo-p7DafpA https://www.youtube.com/watch?v=KSo-p7DafpA
• mhkool 9y ago
  Dear Bill, to spend money wise and efficiently I suggest that you look at the work of Dr Dale Bredesen. Dr Bredesen has fantastic results with his Alzheimer treatment and has published about it. In short, his treatment cures 9 out of 10 patients with mild Alzheimer. His scientific work is solid and a larger study is currently done. Check it out!
  • hendler 9y ago
    http://newsroom.ucla.edu/releases/memory-loss-associated-with-alzheimers-reversed-for-first-time http://newsroom.ucla.edu/releases/memory-loss-associated-wit...
  • djohnston 9y ago
    I've been interested in his work, but discouraged by the case-report based evidence. Can you link me to this larger study?
    • mhkool 9y ago
      sorry, no link. It was said in a video and I am not 100% sure but I believe that part of the study is done at the Cleveland Clinic.
  • dennis_jeeves 9y ago
    Just glanced over a video of his. It does fit in with what I already know, so he likely has the answer. But good luck with getting it noticed. On an average people will not even investigate simple solutions. Essentially the average human mind rationalizes that it sounds too good/easy to be true. ( and Bill Gates is a very average guy outside his computer/money prowess) They would rather believe authority figures who would come up with the next designer drug which modulates the complex chemical biological pathways to offer modest benefits. Designer drugs also make for good profits. For those who want to check similar approaches google keyword - ketogenic diets and Alzheimer’s
  • everybodyknows 9y ago
    The majority of the successes I've seen on Bredesen's web site were against non-Alzheimer's dementia, caused by infection or nutritional problems.
• Carhughes 9y ago
  I love that Gates is driving money into this needed area. We need new ways of attacking cures and the tech arena should be the driver not science. IMO, traditional science has gotten in the way and their agenda isn't where it needs to be: to find a a cure and save lives (take cancer research for instance).
  • Eridrus 9y ago
    I don't understand why you think tech companies will be any better at this than biomedical companies. All businesses have the same incentives to make things chronic issues (subscription revenue!) rather than curing them.
    • Carhughes 9y ago
      Because I recently read a really interesting story that talked about how science tends to get in the way of real progress. I hope you don't mind me sharing it with you but it struck a real note with me. http://www.thenewatlantis.com/publications/saving-science http://www.thenewatlantis.com/publications/saving-science
• amelius 9y ago
  > We need to use data better. Every time a pharmaceutical company or a research lab does a study, they gather lots of information. We should compile this data in a common form [...] We could use all sorts of data, not just from research or pharmaceutical companies. Is there an overview of what data is available or planned for, from clinical to commercial? And what data-integration platforms are planned for? I suspect many countries are trying to invent this on their own, while a world-wide approach could yield better results.
  • komali2 9y ago
    How do you motivate a pharmaceutical company to share R&D they spent millions acquiring?
    • nitrogen 9y ago
      Require it for FDA approval
      • mark-r 9y ago
        The flaw in that plan is that they'll share it in the most unhelpful way possible. See: Patents.
        • amelius 9y ago
          Solution: let the data gathering be done by the FDA (or subsidiary).
• knodi 9y ago
  Alzheimer is essentially type 3 diabetes. I'm happy to see Gates behind this.
  • richardwhiuk 9y ago
    What?
    • arikr 9y ago
      I'm guessing they mean because it may be related to insulin resistance / sugar consumption, but I'm not sure.
• nonbel 9y ago
  Emphasis added: >"Most drug trials to date have targeted amyloid and tau, two proteins that cause plaques and tangles in the brain." This is assumption, not fact: https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-014-0169-0 https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-...
• marze 9y ago
  Say you had a $80 million dollar budget. How would you deploy it to have maximum impact on Alzheimer’s? In other words, what would you do if you were in Gates position?