23 ms·

What causes Alzheimer's? Scientists are rethinking the answer

300 points by i13e 4y ago

vaporup 4y ago
- sugar - carbs - vaccines - big pharma - chemtrails - ...
chaimanmeow 4y ago
So the take away here is that it's looking like the leading or up-and-coming theory now is that this is a recycling waste disposal problem within some cells in the brain, i.e. in the endosomal network? https://en.wikipedia.org/wiki/Endosome https://en.wikipedia.org/wiki/Endosome ??
Jipazgqmnm 4y ago
TLDR: After decades of research focused on the amyloid cascade hypothesis, which claims that sticky plaques of amyloid-beta proteins between neurons are the main cause of Alzheimer's disease, many scientists are now turning their attention to deeper dysfunctions happening within cells. Some believe that the disease is caused by a variety of proteins that may be causing multiple cell dysfunctions, while others are focusing on the role of tau protein tangles, which also form inside neurons.
pfd1986 4y ago
Idea: I'd love a ChatGPT plugin that turns long articles like this into bullet points. Not because I'm lazy and can't read long articles anymore (omg the attention span of young people!). Having worked in this field, I'd love to skim and find out whether there's any new information here I'm not aware of without going to filler paragraphs starting with "in a sunny afternoon in August".
resuresu 4y ago
I liken the fight against alzheimers to the fight against aging. Isn’t it kinda the same battle? As things and people age they just break down, same thing happens to a car, as it gets older the metal rusts, the moving parts seize up and eventually the car itself suffers a catastrophic failure that ultimately results in its death. Same thing happens to people as well, the brain is like an computer in a way, except it does have actual things moving inside of it, the moving parts (Cells) get older and start to break down, ultimately leading to the death of the person.
deleted 4y ago
[deleted]
martin82 4y ago
Carbs cause Alzheimers. As you age, your insulin resistance rises, but you still eat the same amount (or more) of carbs while simultaneously exercising far less. Eat a ketogenic diet and you don't have to worry about Alzheimers.
- zodiakzz 4y ago
  Citation? This kind of study will take at least three quarters of a century to reach such clear cut conclusions. I don't think people hanging on to pseudoscientific BS live long enough to worry about Alzheimers.
scubadude 4y ago
I think there's a social element to it. My mother's cognition fell off a cliff with the social isolation during covid. Also, she has lifetime poor hearing "... mild hearing loss doubled dementia risk. Moderate loss tripled risk, and people with a severe hearing impairment were five times more likely to develop dementia". https://www.hopkinsmedicine.org/health/wellness-and-prevention/the-hidden-risks-of-hearing-loss https://www.hopkinsmedicine.org/health/wellness-and-preventi...
g42gregory 4y ago
In many scientific research projects the same dangerous theme keeps surfacing: monolithic thinking, with “no alternatives allowed”. I feel this is very detrimental to both scientific progress as well as to the broader society.
- naasking 4y ago
  > the same dangerous theme keeps surfacing: dangerous theme keeps surfacing: monolithic thinking, with “no alternatives allowed” That might be part of it. I think a bigger part is, "we don't know what X is so we can't measure it, but Y seems to coincide with X and we can measure Y, so let's focus on Y". This probably happens a lot and sometimes it works out, but it also often doesn't. It failed with dietary cholesterol, and Alzheimer's is the just the latest big failure of this approach.
- simmerup 4y ago
  You'd think that after a decade of failed results, someone would go back to the drawing board and start again. But it never seems to happen.
  - Tagbert 4y ago
    We have only recently had any drugs that could reduce the beta amyloid. While they do reduce the amyloid, they do not see to have an equivalent impact on the actual disease. That failure IS prompting people to reconsider other root causes, again.
- clairity 4y ago
  that's true for any sociopolitical system, and the reason why i push back on dichotomous thinking, especially "left-right" or "democrat-republican" in political discussions. this is the central exploration of Wisdom of Crowds, which i recommend to everyone even though it's considered 'old' now.
- jackmott 4y ago
- 4y ago
eganist 4y ago
Deeper reading into one such alternative: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660461/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660461/ There's a follow-up study on the herpes angle currently in progress (https://www.alzheimers.gov/clinical-trials/valacyclovir-mild-alzheimers-disease https://www.alzheimers.gov/clinical-trials/valacyclovir-mild...) after this one (https://link.springer.com/article/10.1007/s13311-018-0611-x https://link.springer.com/article/10.1007/s13311-018-0611-x) in Taiwan, for instance.
wwwtyro 4y ago
I'm fine with most researchers pursuing a particular direction, but I get concerned when incentives align that provide a significant pressure for them to research what they wouldn't naturally want to research. It seems like there should be a distribution of research directions, not everyone in lockstep. It's hard to gauge from the outside to what degree that is happening in our research institutions today.
- Aperocky 4y ago
  This is what it is: Academic Ponzi Scheme. It just have a longer life than normal ponzi schemes, but ends up in the same way in about 20-40 years.
- resoluteteeth 4y ago
  > when incentives align that provide a significant pressure for them to research what they wouldn't naturally want to research The thing is, the beta amyloid theory was the only explanation for Alzheimer's that would allow treatments to be developed right now. Tons of people want treatments asap. While it makes no sense to develop treatments based on this theory if they definitely won't work, when it looks like there's an 80% chance of the theory being wrong, 100% of drug companies' Alzheimer's drug development money is still going to go to drugs based on this theory because we have nothing else except vague hypotheses with no drug targets. So actually part of the problem is that so many people are incentivized to keep sticking to this theory and someone needs to step in and stop it.
- BeFlatXIII 4y ago
  I’d blame the grant-givers for incentivizing the lockstep behavior rather than the scientists for playing the game.
- caycep 4y ago
  In theory, that's where a lot of individual NIH grants are supposed to do - K level and R level grants. However, NIH people tend to have gotten risk adverse so they look to certain parameter to "vet" whoever gets the money amongst all sorts of applications. The idea is one thing, but also - whose lab you're being mentored in, prior funding success, etc etc play an equal if not more important role. I think the problem then is...if you have some promising directions from preliminary work, to test an idea in clinical trials, it is not cheap. You have to hire a large army of clinicians, nurses, research people, etc etc to manage all the patients/subjects x 10,000 or 50,000. So there has to be at least some politicking to steer where all the research funds go to. And people who are better at "finessing" scientific review boards tend to bubble to the top
optimalsolver 4y ago
...again.
zfi20921 4y ago
Was there ever an examination of this[1]? I'm somewhat confused about how such a long article never mentioned it... [1]: https://www.theguardian.com/society/2022/jul/23/alzheimers-study-fraudulent https://www.theguardian.com/society/2022/jul/23/alzheimers-s...
- carls 4y ago
  The article does in fact mention this event in the below paragraph: "The hypothesis took another hit last July when a bombshell article in Science revealed that data in the influential 2006 Nature paper linking amyloid plaques to cognitive symptoms of Alzheimer’s disease may have been fabricated. The connection claimed by the paper had convinced many researchers to keep pursuing amyloid theories at the time. For many of them, the new exposé created a “big dent” in the amyloid theory, Patira said."
kyaghmour 4y ago
As someone who has a close relative diagnosed with this disease, I'm always on the lookout for new information. So this is interesting. One area I'm particularly interested in is the correlation to diabetes. It's a factor that I found being mentioned here and there in some references. In the immediate case that interests me, there's a 20+ year history of type 2 diabetes and a recent scan showed severe bilateral hypocampal atrophy. When googling for a link between the two I found this: "Lower insulin secretion was significantly associated with HPGA (hippocampal and parahippocampal gyrus atrophy) in patients with type 2 diabetes mellitus. The results of this study support the hypothesis that insulin‐signaling abnormalities are involved in the pathophysiology of Alzheimer’s disease." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504906/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504906/ Yet, the mechanism of this, if indeed there's causality (not just correlation) does not seem to be known.
- lofaszvanitt 4y ago
  Yudkin wrote the book about sugars Pure, White and Deadly in 1972. EMPHASIS: 1972! 50 years ago. And processed foods is everywhere. And people are wondering why we have diabetes and possibly brain diabetes that is Alzheimer's.
- hnthrowaway8493 4y ago
  It doesn't directly contradict the paper you linked, but figured it's worth mentioning - the hypothesis about a diabetes-Alzheimer's link might have originally stemmed from fraudulent work. From the "related story" at the bottom of the linked Science article about fraud https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease https://www.science.org/content/article/potential-fabricatio... (related story is titled "Research backing experimental Alzheimer’s drug was first target of suspicion", also available in their reader here: https://www.science.org/doi/full/10.1126/science.ade0181?adobe_mc=MCMID%3D81822615985399127293767217257181301656%7CMCORGID%3D242B6472541199F70A4C98A6%2540AdobeOrg%7CTS%3D1670791362 https://www.science.org/doi/full/10.1126/science.ade0181?ado...) > The most influential Cassava-related paper appeared in The Journal of Clinical Investigation in 2012. The authors—including Wang; Arnold; David Bennett, who leads a brain-tissue bank at Rush University; and his Rush colleague, neuroscientist Zoe Arvanitakis—linked insulin resistance to Alzheimer’s and the formation of amyloid plaques. Cassava scientists say Simufilam lessens insulin resistance. They relied on a method in which dead brain tissue, frozen for a decade and then partially thawed and chopped, purportedly generates chemical signals. > Schrag and others say it contradicts basic neurobiology. Schrag adds that he could find no evidence that other investigators have replicated that result. (None of the authors agreed to be interviewed for this article.) > That paper supported the science behind Simufilam, Schrag says, “and spawned an entire field of research in Alzheimer’s, ‘diabetes of the brain.’” It has been cited more than 1500 times. Schrag sent the journal’s editor his analysis of more than 15 suspect images in two groups. The editor says the journal analyzed high-resolution versions of the images in the first group. It could not corroborate his findings and therefore did not investigate further.
chami114 4y ago
this is a good article to spotlight on..
snshn 4y ago
could be prions from eating meat, could be genetic... it's likely similar to "what causes cancer?"
- ethanbond 4y ago
  AFAIK Alzheimer’s is a single disease, whereas cancer is kind of a catch-all category for a huuuuge set of different disorders caused and treated by different things.
  - pedalpete 4y ago
    Alzheimer's is currently categorized as a single disease. But I suspect the result will turn out to be similar to Ulcers which were initially thought to be the result of acid diets, and predisposed conditions, but turns out there are many types, and the most common type is bacterial. I think we'll find there are many types of Alzheimer's, some Amyloid based, others viral, or dietary, etc.
- TheSpiceIsLife 4y ago
  I wanted to argue against this, but the strongest interpretation of what your saying could hold up to reason. Perhaps there are some kinds of prions, or other, maybe similar, infectious agents, we haven't isolated yet.
  - snshn 4y ago
    I think it's extremely likely it's caused by something either unknown or previously considered to be safe for humans. Would be nice to study groups of people and see their rates of this illness. Multi-group elimination diet, with HTMA and blood and bone marrow tested for presence of metals, oxidants, etc.
    - TheSpiceIsLife 4y ago
      I'd like to assume epidemiologists are all over this?
macrolime 4y ago
There's a couple clinical trials with various variations of young blood or blood plasma being given to Alzheimer's patients. Should be interesting to see how that goes.
- jcampbell1 4y ago
  Did Peter Theil fund this research?
  - macrolime 4y ago
    Not sure who's funding what Most recent one I saw is this one that I think is funded by the Norwegian government https://bmjopen.bmj.com/content/12/9/e056964 https://bmjopen.bmj.com/content/12/9/e056964 Then there's startups like Alkahest https://www.alkahest.com/pipeline/akst-grf6019/ https://www.alkahest.com/pipeline/akst-grf6019/ Clinical trials of sorts has been going on since at least 2017 https://www.nature.com/articles/nature.2017.22930 https://www.nature.com/articles/nature.2017.22930
    - jcampbell1 4y ago
      It was a joke as Peter Theil has been jokingly called a vampire because he gets blood transfusions from young people in an effort to maintain his youth. That being said, thanks for the links. I read them all. Here is the results of the Phase II from Alkahest. Not a game changer thus far. https://www.alzforum.org/therapeutics/grf6019 https://www.alzforum.org/therapeutics/grf6019
stevev 4y ago
Tylenol
- DiggyJohnson 4y ago
  What about it?
- Zigurd 4y ago
  Acetaminophen has numerous well-known risks and is probably more dangerous than most people appreciate, and is overused, over-marketed, and too-readily available. BUT, like some other too-simple hypotheses on this thread, it isn't giving you Alzheimer's directly. It may be part of a complex network of causes. Or not.
dang 4y ago
There are too many Alzheimer's threads to list but these seem to be the ones related to the amyloid hypothesis: Decreased proteins, not amyloid plaques, tied to Alzheimer's disease - https://news.ycombinator.com/item?id=33096228 https://news.ycombinator.com/item?id=33096228 - Oct 2022 (3 comments) A Positive Amyloid Trial, Finally? - https://news.ycombinator.com/item?id=33010078 https://news.ycombinator.com/item?id=33010078 - Sept 2022 (49 comments) Faked Beta-Amyloid Data. What Does It Mean? - https://news.ycombinator.com/item?id=32224823 https://news.ycombinator.com/item?id=32224823 - July 2022 (168 comments) Two decades of Alzheimer’s research was based on deliberate fraud - https://news.ycombinator.com/item?id=32212719 https://news.ycombinator.com/item?id=32212719 - July 2022 (298 comments) Potential fabrication in research threatens the amyloid theory of Alzheimer’s - https://news.ycombinator.com/item?id=32183302 https://news.ycombinator.com/item?id=32183302 - July 2022 (256 comments) 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) Tau PET imaging beats amyloid-based approach in battle against Alzheimer’s - https://news.ycombinator.com/item?id=21970903 https://news.ycombinator.com/item?id=21970903 - Jan 2020 (15 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) Robert Moir, 58, Dies; His Research Changed Views on Alzheimer’s - https://news.ycombinator.com/item?id=21859212 https://news.ycombinator.com/item?id=21859212 - Dec 2019 (3 comments) Why Do We Keep Investing in Anti-Amyloid Therapies for Alzheimer’s Disease? - https://news.ycombinator.com/item?id=19496402 https://news.ycombinator.com/item?id=19496402 - March 2019 (1 comment) Alzheimer’s Drug Failure Leaves Scientists Seeking New Direction - https://news.ycombinator.com/item?id=19468987 https://news.ycombinator.com/item?id=19468987 - March 2019 (76 comments) Scientists discover why many Alzheimer’s drugs fail, identify one that may work - https://news.ycombinator.com/item?id=18030200 https://news.ycombinator.com/item?id=18030200 - Sept 2018 (9 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) Researcher says we have Alzheimer's wrong - https://news.ycombinator.com/item?id=9509808 https://news.ycombinator.com/item?id=9509808 - May 2015 (27 comments) An Outcast Among Peers Gains Traction on Alzheimer's Cure - https://news.ycombinator.com/item?id=4766983 https://news.ycombinator.com/item?id=4766983 - Nov 2012 (11 comments)
torben-friis 4y ago
Has anyone noticed that Alzheimer’s research tend to hit the front page much more than other medical news? I’ve been wondering why for a while.
- runjake 4y ago
  Because it's a particularly terrifying and relatively untreatable killer.
  - throwayyy479087 4y ago
    *completely untreatable killer
- pvaldes 4y ago
  Is one of the five or six big medical problems of our time.
  - mongol 4y ago
    You are probably right. How would a list look like? In no particular order, perhaps: Cancer ALS Alzheimer Diabetes Covid AIDS ?
    - ebiester 4y ago
      Heart Disease, Cancer, Stroke, Alzheimer's, and Diabetes would be an easy top 5. Covid was the third leading cause of death last year, and considering the effects on some, it likely deserves more work as well. source: https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm
    - hollerith 4y ago
      You left out the biggest killer: heart disease.
      - throwayyy479087 4y ago
DoreenMichele 4y ago
The brain "takes out the trash" when you sleep.* From what I have read, the accumulation of both amyloid beta and tau are linked to sleep deprivation. They may be markers of sleep deprivation and treating the sleep deprivation may be the best thing to do, though that probably won't get someone famous for some billion dollar drug discovery, so no one will likely pursue it. (Yes, I am aware that some of the research is possibly fraud, other avenues of investigation have been suppressed, etc. I've read quite a few articles about Alzheimer's, my late father had Alzheimer's and ...etc.) * https://news.ycombinator.com/item?id=25427090 https://news.ycombinator.com/item?id=25427090
- manmal 4y ago
  Disturbed sleep should IMO also be looked at - eg UARS and sleep apnea. You can sleep 8h every night and still feel crappy waking up. Maybe disturbed sleep is even worse than lack of sleep? I can feel better after 6h of good sleep than after 9h of disrupted sleep (eg when I know I‘ve been snoring, eg due to throat infection).
  - pedalpete 4y ago
    The link isn't "disturbed sleep" necessarily. As we age, sleep naturally degrades, and that degradation is in the slow-wave sleep which drives the clearing of amyloid plaques, and tau (along with hormonal response, memory consolidation, nervous system, and more). The technology we're developing at https://soundmind.co https://soundmind.co is supporting an Alzheimer's prevention trial beginning in January '23 which is looking at the impact of slow-wave enhancement in the clearing of Amyloid plaques.
    - manmal 4y ago
      By your argument, everybody would get Alzheimer‘s sooner or later. But most old people (still) don’t.
      - pedalpete 4y ago
        Not necessarily. Though Alzheimer's is an age related disease, and each 5 years increases the likelihood of developing Alzheimer's [1]. The older you get, the more likely you are to get Alzheimer's. Young people don't get Alzheimer's (with the exception of early onset, which is still in an older population). So if we extend life long enough, will everyone get it? Unlikely. Just like not everyone with high cholesterol develop heart disease. However the older we get, the worse sleep gets, the more build up of amyloids, the more likely a person is to develop Alzheimer's. Part of the reason the amyloid theory is in question is because there are people with significant build up of amyloid who do not develop Alzheimer's and there are people with little amyloid build up who do generate Alzheimer's. [1] https://www.nia.nih.gov/health/what-causes-alzheimers-disease#:~:text=Older%20age%20does%20not%20cause,older%20may%20have%20Alzheimer's%20disease https://www.nia.nih.gov/health/what-causes-alzheimers-diseas....
l2silver 4y ago
Did anyone read "The end of Alzheimers" by Dr. Bredesen? In the book he claims to have the cure, but no one has really talked about his approach. Was it debunked? I'm confused.
- SirensOfTitan 4y ago
  Bredesen's protocol is essentially: exercise, sleep, keep your mind engaged, control any correlated issues [like sleep apnea, diabetes], treat correlated infective illness [like EBV] and take some supplements that could positively affect some cause of the illness. I think it's likely that a huge portion of his protocol will prove worthwhile in preventing Alzheimers based on probable causes outside of the AB hypothesis. ... with that all being said, my mother has early onset Alzheimer's disease (hardly over 60), and getting her on any mitigative attempts like elucidated by Bredesen is effectively impossible. She's still independent enough to live and do most things on her own, but injecting new habits has proven really challenging, as apathy is one of the most pervasive symptoms of the disease. She also had years of obstructive sleep apnea that she refused to treat, as she hated the CPAP machine. Sure, Breseden is likely a bit of a scam artist, and it's very unlikely his protocol reverses the illness as he claims, but his ideas piecemeal are hardly "unproven" as elucidated by folks here. I think it's very unlikely that Alzheimer's finds a "cure" in a pill or some easy treatment--it seems like it's a disease that emerges after years of dysfunction, potentially from many causes, and you can't rebuild Rome overnight. I'd guess that the future of Alzheimer's research will be in prevention.
- wutheringh 4y ago
  No one talks about it because it’s too ridiculous to be taken seriously by anyone with credentials
  - l2silver 4y ago
    What's ridiculous about it?
    - wutheringh 4y ago
personalityson 4y ago
"Scientists researching possible candidates for treating Alzheimer's disease found exercise outperformed all tested drugs for the ability to reverse dysregulated gene expression." https://www.nature.com/articles/s41598-022-22179-z https://www.nature.com/articles/s41598-022-22179-z "High fitness in middle age reduces the chance of dementia by ninety percent" https://www.ergo-log.com/high-fitness-in-middle-age-reduces-chance-of-dementia-by-ninety-percent.html https://www.ergo-log.com/high-fitness-in-middle-age-reduces-...
- m463 4y ago
  also saunas.
- JamesBarney 4y ago
  They don't know high fitness reduces chances of dementia they just know it's associated with it. I imagine people who are naturally healthier probably more fit and less demented.
- steve_adams_86 4y ago
  Not to be pedantic, but the number appears to be (up to) 88%, and the study involved women only. Incredible results but I think the specifics are worth using when they’re available. Also, there is no cause and effect here, though vascular origin dementia as noted seems almost certainly to be reduced by better cardiovascular fitness, as are many other vascular issues. Having said that, vascular and arterial lining damage due to diet appears not to be resolved by exercise, and could very easily be a culprit here as well. Fitness is a great tool for general well-being, but it doesn’t appear to be the singular cause of increased wellness here.
  - deleted 4y ago
    [deleted]
  - siftrics 4y ago
    That is a ludicrous take. If exercise reduced risk of dementia by 99% would you still feel compelled to point out that it "doesn't appear to be the singular cause of increased wellness"? Where's your threshold? We literally have the solution. What you're saying, while it is technically true, seems to be more of an excuse or justification not to exercise. Perhaps I'm reading too much into your comment.
andrewflnr 4y ago
> Faced with the choice of either chasing cures based on amyloid or pursuing a nebulous something-more-than-amyloid, the medical and pharmaceutical communities made what seemed like the rational choice. No one should accept this as an excuse. They weren't rational, they chased the shiny. I'm not sure "visibility bias" already has the right meaning, but if not we need a term for this pervasive problem where people just choose to not believe or otherwise ignore factors that don't leap out to them, even if they're just as if not more important in reality. More abstractly we see it with Alzheimer's hypotheses here: Hypotheses with greater uncertainty suffer the same treatment, where not having as clear an idea about what it is causes it to be entirely discounted, for years, in favor of the clearer action plan.
jleyank 4y ago
Remember they need new ideas and then they need animal models with which they can test these new ideas. They had one, they had drug candidates that satisfied the model and yet nothing happened. We’ve just seen the various tries run down and smell the smoke of billions of dollars burning to ash. It’s research not engineering and we can’t experiment on people. Huge unmet market need will keep companies trying.
mikenew 4y ago
There's a lot of articles recently on how we're "rethinking" Alzheimer's, and what is utterly baffling to me is the way none of them seem to mention that it has recently come to light that much of the foundational research on Alzheimer's was falsified: https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease https://www.science.org/content/article/potential-fabricatio...
- alexfromapex 4y ago
  And they mention the “resistance” in the scientific community to consider causes other than amyloids which is introducing human biases into the scientific process
- UncombedCoconut 4y ago
  Great news: this article does discuss it. It links to that exact Science paper.

300 points by i13e 4y ago

- sugar - carbs - vaccines - big pharma - chemtrails - ...

So the take away here is that it's looking like the leading or up-and-coming theory now is that this is a recycling waste disposal problem within some cells in the brain, i.e. in the endosomal network? https://en.wikipedia.org/wiki/Endosome https://en.wikipedia.org/wiki/Endosome ??

Jipazgqmnm 4y ago

TLDR: After decades of research focused on the amyloid cascade hypothesis, which claims that sticky plaques of amyloid-beta proteins between neurons are the main cause of Alzheimer's disease, many scientists are now turning their attention to deeper dysfunctions happening within cells. Some believe that the disease is caused by a variety of proteins that may be causing multiple cell dysfunctions, while others are focusing on the role of tau protein tangles, which also form inside neurons.

pfd1986 4y ago

Idea: I'd love a ChatGPT plugin that turns long articles like this into bullet points. Not because I'm lazy and can't read long articles anymore (omg the attention span of young people!). Having worked in this field, I'd love to skim and find out whether there's any new information here I'm not aware of without going to filler paragraphs starting with "in a sunny afternoon in August".

resuresu 4y ago

I liken the fight against alzheimers to the fight against aging. Isn’t it kinda the same battle? As things and people age they just break down, same thing happens to a car, as it gets older the metal rusts, the moving parts seize up and eventually the car itself suffers a catastrophic failure that ultimately results in its death. Same thing happens to people as well, the brain is like an computer in a way, except it does have actual things moving inside of it, the moving parts (Cells) get older and start to break down, ultimately leading to the death of the person.

deleted 4y ago

[deleted]

martin82 4y ago

Carbs cause Alzheimers. As you age, your insulin resistance rises, but you still eat the same amount (or more) of carbs while simultaneously exercising far less. Eat a ketogenic diet and you don't have to worry about Alzheimers.

zodiakzz 4y ago
Citation? This kind of study will take at least three quarters of a century to reach such clear cut conclusions. I don't think people hanging on to pseudoscientific BS live long enough to worry about Alzheimers.

scubadude 4y ago

I think there's a social element to it. My mother's cognition fell off a cliff with the social isolation during covid. Also, she has lifetime poor hearing "... mild hearing loss doubled dementia risk. Moderate loss tripled risk, and people with a severe hearing impairment were five times more likely to develop dementia". https://www.hopkinsmedicine.org/health/wellness-and-prevention/the-hidden-risks-of-hearing-loss https://www.hopkinsmedicine.org/health/wellness-and-preventi...

g42gregory 4y ago

In many scientific research projects the same dangerous theme keeps surfacing: monolithic thinking, with “no alternatives allowed”. I feel this is very detrimental to both scientific progress as well as to the broader society.

naasking 4y ago
> the same dangerous theme keeps surfacing: dangerous theme keeps surfacing: monolithic thinking, with “no alternatives allowed” That might be part of it. I think a bigger part is, "we don't know what X is so we can't measure it, but Y seems to coincide with X and we can measure Y, so let's focus on Y". This probably happens a lot and sometimes it works out, but it also often doesn't. It failed with dietary cholesterol, and Alzheimer's is the just the latest big failure of this approach.
simmerup 4y ago
You'd think that after a decade of failed results, someone would go back to the drawing board and start again. But it never seems to happen.
- Tagbert 4y ago
  We have only recently had any drugs that could reduce the beta amyloid. While they do reduce the amyloid, they do not see to have an equivalent impact on the actual disease. That failure IS prompting people to reconsider other root causes, again.
clairity 4y ago
that's true for any sociopolitical system, and the reason why i push back on dichotomous thinking, especially "left-right" or "democrat-republican" in political discussions. this is the central exploration of Wisdom of Crowds, which i recommend to everyone even though it's considered 'old' now.
jackmott 4y ago
4y ago

eganist 4y ago

Deeper reading into one such alternative: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660461/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660461/ There's a follow-up study on the herpes angle currently in progress (https://www.alzheimers.gov/clinical-trials/valacyclovir-mild-alzheimers-disease https://www.alzheimers.gov/clinical-trials/valacyclovir-mild...) after this one (https://link.springer.com/article/10.1007/s13311-018-0611-x https://link.springer.com/article/10.1007/s13311-018-0611-x) in Taiwan, for instance.

wwwtyro 4y ago

I'm fine with most researchers pursuing a particular direction, but I get concerned when incentives align that provide a significant pressure for them to research what they wouldn't naturally want to research. It seems like there should be a distribution of research directions, not everyone in lockstep. It's hard to gauge from the outside to what degree that is happening in our research institutions today.

Aperocky 4y ago
This is what it is: Academic Ponzi Scheme. It just have a longer life than normal ponzi schemes, but ends up in the same way in about 20-40 years.
resoluteteeth 4y ago
> when incentives align that provide a significant pressure for them to research what they wouldn't naturally want to research The thing is, the beta amyloid theory was the only explanation for Alzheimer's that would allow treatments to be developed right now. Tons of people want treatments asap. While it makes no sense to develop treatments based on this theory if they definitely won't work, when it looks like there's an 80% chance of the theory being wrong, 100% of drug companies' Alzheimer's drug development money is still going to go to drugs based on this theory because we have nothing else except vague hypotheses with no drug targets. So actually part of the problem is that so many people are incentivized to keep sticking to this theory and someone needs to step in and stop it.
BeFlatXIII 4y ago
I’d blame the grant-givers for incentivizing the lockstep behavior rather than the scientists for playing the game.
caycep 4y ago
In theory, that's where a lot of individual NIH grants are supposed to do - K level and R level grants. However, NIH people tend to have gotten risk adverse so they look to certain parameter to "vet" whoever gets the money amongst all sorts of applications. The idea is one thing, but also - whose lab you're being mentored in, prior funding success, etc etc play an equal if not more important role. I think the problem then is...if you have some promising directions from preliminary work, to test an idea in clinical trials, it is not cheap. You have to hire a large army of clinicians, nurses, research people, etc etc to manage all the patients/subjects x 10,000 or 50,000. So there has to be at least some politicking to steer where all the research funds go to. And people who are better at "finessing" scientific review boards tend to bubble to the top

optimalsolver 4y ago

...again.

zfi20921 4y ago

Was there ever an examination of this[1]? I'm somewhat confused about how such a long article never mentioned it... [1]: https://www.theguardian.com/society/2022/jul/23/alzheimers-study-fraudulent https://www.theguardian.com/society/2022/jul/23/alzheimers-s...

carls 4y ago
The article does in fact mention this event in the below paragraph: "The hypothesis took another hit last July when a bombshell article in Science revealed that data in the influential 2006 Nature paper linking amyloid plaques to cognitive symptoms of Alzheimer’s disease may have been fabricated. The connection claimed by the paper had convinced many researchers to keep pursuing amyloid theories at the time. For many of them, the new exposé created a “big dent” in the amyloid theory, Patira said."

kyaghmour 4y ago

As someone who has a close relative diagnosed with this disease, I'm always on the lookout for new information. So this is interesting. One area I'm particularly interested in is the correlation to diabetes. It's a factor that I found being mentioned here and there in some references. In the immediate case that interests me, there's a 20+ year history of type 2 diabetes and a recent scan showed severe bilateral hypocampal atrophy. When googling for a link between the two I found this: "Lower insulin secretion was significantly associated with HPGA (hippocampal and parahippocampal gyrus atrophy) in patients with type 2 diabetes mellitus. The results of this study support the hypothesis that insulin‐signaling abnormalities are involved in the pathophysiology of Alzheimer’s disease." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504906/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504906/ Yet, the mechanism of this, if indeed there's causality (not just correlation) does not seem to be known.

lofaszvanitt 4y ago
Yudkin wrote the book about sugars Pure, White and Deadly in 1972. EMPHASIS: 1972! 50 years ago. And processed foods is everywhere. And people are wondering why we have diabetes and possibly brain diabetes that is Alzheimer's.
hnthrowaway8493 4y ago
It doesn't directly contradict the paper you linked, but figured it's worth mentioning - the hypothesis about a diabetes-Alzheimer's link might have originally stemmed from fraudulent work. From the "related story" at the bottom of the linked Science article about fraud https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease https://www.science.org/content/article/potential-fabricatio... (related story is titled "Research backing experimental Alzheimer’s drug was first target of suspicion", also available in their reader here: https://www.science.org/doi/full/10.1126/science.ade0181?adobe_mc=MCMID%3D81822615985399127293767217257181301656%7CMCORGID%3D242B6472541199F70A4C98A6%2540AdobeOrg%7CTS%3D1670791362 https://www.science.org/doi/full/10.1126/science.ade0181?ado...) > The most influential Cassava-related paper appeared in The Journal of Clinical Investigation in 2012. The authors—including Wang; Arnold; David Bennett, who leads a brain-tissue bank at Rush University; and his Rush colleague, neuroscientist Zoe Arvanitakis—linked insulin resistance to Alzheimer’s and the formation of amyloid plaques. Cassava scientists say Simufilam lessens insulin resistance. They relied on a method in which dead brain tissue, frozen for a decade and then partially thawed and chopped, purportedly generates chemical signals. > Schrag and others say it contradicts basic neurobiology. Schrag adds that he could find no evidence that other investigators have replicated that result. (None of the authors agreed to be interviewed for this article.) > That paper supported the science behind Simufilam, Schrag says, “and spawned an entire field of research in Alzheimer’s, ‘diabetes of the brain.’” It has been cited more than 1500 times. Schrag sent the journal’s editor his analysis of more than 15 suspect images in two groups. The editor says the journal analyzed high-resolution versions of the images in the first group. It could not corroborate his findings and therefore did not investigate further.

chami114 4y ago

this is a good article to spotlight on..

snshn 4y ago

could be prions from eating meat, could be genetic... it's likely similar to "what causes cancer?"

ethanbond 4y ago
AFAIK Alzheimer’s is a single disease, whereas cancer is kind of a catch-all category for a huuuuge set of different disorders caused and treated by different things.
- pedalpete 4y ago
  Alzheimer's is currently categorized as a single disease. But I suspect the result will turn out to be similar to Ulcers which were initially thought to be the result of acid diets, and predisposed conditions, but turns out there are many types, and the most common type is bacterial. I think we'll find there are many types of Alzheimer's, some Amyloid based, others viral, or dietary, etc.
TheSpiceIsLife 4y ago
I wanted to argue against this, but the strongest interpretation of what your saying could hold up to reason. Perhaps there are some kinds of prions, or other, maybe similar, infectious agents, we haven't isolated yet.
- snshn 4y ago
  I think it's extremely likely it's caused by something either unknown or previously considered to be safe for humans. Would be nice to study groups of people and see their rates of this illness. Multi-group elimination diet, with HTMA and blood and bone marrow tested for presence of metals, oxidants, etc.
  - TheSpiceIsLife 4y ago
    I'd like to assume epidemiologists are all over this?

macrolime 4y ago

There's a couple clinical trials with various variations of young blood or blood plasma being given to Alzheimer's patients. Should be interesting to see how that goes.

jcampbell1 4y ago
Did Peter Theil fund this research?
- macrolime 4y ago
  Not sure who's funding what Most recent one I saw is this one that I think is funded by the Norwegian government https://bmjopen.bmj.com/content/12/9/e056964 https://bmjopen.bmj.com/content/12/9/e056964 Then there's startups like Alkahest https://www.alkahest.com/pipeline/akst-grf6019/ https://www.alkahest.com/pipeline/akst-grf6019/ Clinical trials of sorts has been going on since at least 2017 https://www.nature.com/articles/nature.2017.22930 https://www.nature.com/articles/nature.2017.22930
  - jcampbell1 4y ago
    It was a joke as Peter Theil has been jokingly called a vampire because he gets blood transfusions from young people in an effort to maintain his youth. That being said, thanks for the links. I read them all. Here is the results of the Phase II from Alkahest. Not a game changer thus far. https://www.alzforum.org/therapeutics/grf6019 https://www.alzforum.org/therapeutics/grf6019

stevev 4y ago

Tylenol

DiggyJohnson 4y ago
What about it?
Zigurd 4y ago
Acetaminophen has numerous well-known risks and is probably more dangerous than most people appreciate, and is overused, over-marketed, and too-readily available. BUT, like some other too-simple hypotheses on this thread, it isn't giving you Alzheimer's directly. It may be part of a complex network of causes. Or not.

dang 4y ago

There are too many Alzheimer's threads to list but these seem to be the ones related to the amyloid hypothesis: Decreased proteins, not amyloid plaques, tied to Alzheimer's disease - https://news.ycombinator.com/item?id=33096228 https://news.ycombinator.com/item?id=33096228 - Oct 2022 (3 comments) A Positive Amyloid Trial, Finally? - https://news.ycombinator.com/item?id=33010078 https://news.ycombinator.com/item?id=33010078 - Sept 2022 (49 comments) Faked Beta-Amyloid Data. What Does It Mean? - https://news.ycombinator.com/item?id=32224823 https://news.ycombinator.com/item?id=32224823 - July 2022 (168 comments) Two decades of Alzheimer’s research was based on deliberate fraud - https://news.ycombinator.com/item?id=32212719 https://news.ycombinator.com/item?id=32212719 - July 2022 (298 comments) Potential fabrication in research threatens the amyloid theory of Alzheimer’s - https://news.ycombinator.com/item?id=32183302 https://news.ycombinator.com/item?id=32183302 - July 2022 (256 comments) 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) Tau PET imaging beats amyloid-based approach in battle against Alzheimer’s - https://news.ycombinator.com/item?id=21970903 https://news.ycombinator.com/item?id=21970903 - Jan 2020 (15 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) Robert Moir, 58, Dies; His Research Changed Views on Alzheimer’s - https://news.ycombinator.com/item?id=21859212 https://news.ycombinator.com/item?id=21859212 - Dec 2019 (3 comments) Why Do We Keep Investing in Anti-Amyloid Therapies for Alzheimer’s Disease? - https://news.ycombinator.com/item?id=19496402 https://news.ycombinator.com/item?id=19496402 - March 2019 (1 comment) Alzheimer’s Drug Failure Leaves Scientists Seeking New Direction - https://news.ycombinator.com/item?id=19468987 https://news.ycombinator.com/item?id=19468987 - March 2019 (76 comments) Scientists discover why many Alzheimer’s drugs fail, identify one that may work - https://news.ycombinator.com/item?id=18030200 https://news.ycombinator.com/item?id=18030200 - Sept 2018 (9 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) Researcher says we have Alzheimer's wrong - https://news.ycombinator.com/item?id=9509808 https://news.ycombinator.com/item?id=9509808 - May 2015 (27 comments) An Outcast Among Peers Gains Traction on Alzheimer's Cure - https://news.ycombinator.com/item?id=4766983 https://news.ycombinator.com/item?id=4766983 - Nov 2012 (11 comments)

torben-friis 4y ago

Has anyone noticed that Alzheimer’s research tend to hit the front page much more than other medical news? I’ve been wondering why for a while.

runjake 4y ago
Because it's a particularly terrifying and relatively untreatable killer.
- throwayyy479087 4y ago
  *completely untreatable killer
pvaldes 4y ago
Is one of the five or six big medical problems of our time.
- mongol 4y ago
  You are probably right. How would a list look like? In no particular order, perhaps: Cancer ALS Alzheimer Diabetes Covid AIDS ?
  - ebiester 4y ago
    Heart Disease, Cancer, Stroke, Alzheimer's, and Diabetes would be an easy top 5. Covid was the third leading cause of death last year, and considering the effects on some, it likely deserves more work as well. source: https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm
  - hollerith 4y ago
    You left out the biggest killer: heart disease.
    - throwayyy479087 4y ago

DoreenMichele 4y ago

The brain "takes out the trash" when you sleep.* From what I have read, the accumulation of both amyloid beta and tau are linked to sleep deprivation. They may be markers of sleep deprivation and treating the sleep deprivation may be the best thing to do, though that probably won't get someone famous for some billion dollar drug discovery, so no one will likely pursue it. (Yes, I am aware that some of the research is possibly fraud, other avenues of investigation have been suppressed, etc. I've read quite a few articles about Alzheimer's, my late father had Alzheimer's and ...etc.) * https://news.ycombinator.com/item?id=25427090 https://news.ycombinator.com/item?id=25427090

manmal 4y ago
Disturbed sleep should IMO also be looked at - eg UARS and sleep apnea. You can sleep 8h every night and still feel crappy waking up. Maybe disturbed sleep is even worse than lack of sleep? I can feel better after 6h of good sleep than after 9h of disrupted sleep (eg when I know I‘ve been snoring, eg due to throat infection).
- pedalpete 4y ago
  The link isn't "disturbed sleep" necessarily. As we age, sleep naturally degrades, and that degradation is in the slow-wave sleep which drives the clearing of amyloid plaques, and tau (along with hormonal response, memory consolidation, nervous system, and more). The technology we're developing at https://soundmind.co https://soundmind.co is supporting an Alzheimer's prevention trial beginning in January '23 which is looking at the impact of slow-wave enhancement in the clearing of Amyloid plaques.
  - manmal 4y ago
    By your argument, everybody would get Alzheimer‘s sooner or later. But most old people (still) don’t.
    - pedalpete 4y ago
      Not necessarily. Though Alzheimer's is an age related disease, and each 5 years increases the likelihood of developing Alzheimer's [1]. The older you get, the more likely you are to get Alzheimer's. Young people don't get Alzheimer's (with the exception of early onset, which is still in an older population). So if we extend life long enough, will everyone get it? Unlikely. Just like not everyone with high cholesterol develop heart disease. However the older we get, the worse sleep gets, the more build up of amyloids, the more likely a person is to develop Alzheimer's. Part of the reason the amyloid theory is in question is because there are people with significant build up of amyloid who do not develop Alzheimer's and there are people with little amyloid build up who do generate Alzheimer's. [1] https://www.nia.nih.gov/health/what-causes-alzheimers-disease#:~:text=Older%20age%20does%20not%20cause,older%20may%20have%20Alzheimer's%20disease https://www.nia.nih.gov/health/what-causes-alzheimers-diseas....

l2silver 4y ago

Did anyone read "The end of Alzheimers" by Dr. Bredesen? In the book he claims to have the cure, but no one has really talked about his approach. Was it debunked? I'm confused.

SirensOfTitan 4y ago
Bredesen's protocol is essentially: exercise, sleep, keep your mind engaged, control any correlated issues [like sleep apnea, diabetes], treat correlated infective illness [like EBV] and take some supplements that could positively affect some cause of the illness. I think it's likely that a huge portion of his protocol will prove worthwhile in preventing Alzheimers based on probable causes outside of the AB hypothesis. ... with that all being said, my mother has early onset Alzheimer's disease (hardly over 60), and getting her on any mitigative attempts like elucidated by Bredesen is effectively impossible. She's still independent enough to live and do most things on her own, but injecting new habits has proven really challenging, as apathy is one of the most pervasive symptoms of the disease. She also had years of obstructive sleep apnea that she refused to treat, as she hated the CPAP machine. Sure, Breseden is likely a bit of a scam artist, and it's very unlikely his protocol reverses the illness as he claims, but his ideas piecemeal are hardly "unproven" as elucidated by folks here. I think it's very unlikely that Alzheimer's finds a "cure" in a pill or some easy treatment--it seems like it's a disease that emerges after years of dysfunction, potentially from many causes, and you can't rebuild Rome overnight. I'd guess that the future of Alzheimer's research will be in prevention.
wutheringh 4y ago
No one talks about it because it’s too ridiculous to be taken seriously by anyone with credentials
- l2silver 4y ago
  What's ridiculous about it?
  - wutheringh 4y ago

personalityson 4y ago

"Scientists researching possible candidates for treating Alzheimer's disease found exercise outperformed all tested drugs for the ability to reverse dysregulated gene expression." https://www.nature.com/articles/s41598-022-22179-z https://www.nature.com/articles/s41598-022-22179-z "High fitness in middle age reduces the chance of dementia by ninety percent" https://www.ergo-log.com/high-fitness-in-middle-age-reduces-chance-of-dementia-by-ninety-percent.html https://www.ergo-log.com/high-fitness-in-middle-age-reduces-...

m463 4y ago
also saunas.
JamesBarney 4y ago
They don't know high fitness reduces chances of dementia they just know it's associated with it. I imagine people who are naturally healthier probably more fit and less demented.
steve_adams_86 4y ago
Not to be pedantic, but the number appears to be (up to) 88%, and the study involved women only. Incredible results but I think the specifics are worth using when they’re available. Also, there is no cause and effect here, though vascular origin dementia as noted seems almost certainly to be reduced by better cardiovascular fitness, as are many other vascular issues. Having said that, vascular and arterial lining damage due to diet appears not to be resolved by exercise, and could very easily be a culprit here as well. Fitness is a great tool for general well-being, but it doesn’t appear to be the singular cause of increased wellness here.
- deleted 4y ago
  [deleted]
- siftrics 4y ago
  That is a ludicrous take. If exercise reduced risk of dementia by 99% would you still feel compelled to point out that it "doesn't appear to be the singular cause of increased wellness"? Where's your threshold? We literally have the solution. What you're saying, while it is technically true, seems to be more of an excuse or justification not to exercise. Perhaps I'm reading too much into your comment.

andrewflnr 4y ago

> Faced with the choice of either chasing cures based on amyloid or pursuing a nebulous something-more-than-amyloid, the medical and pharmaceutical communities made what seemed like the rational choice. No one should accept this as an excuse. They weren't rational, they chased the shiny. I'm not sure "visibility bias" already has the right meaning, but if not we need a term for this pervasive problem where people just choose to not believe or otherwise ignore factors that don't leap out to them, even if they're just as if not more important in reality. More abstractly we see it with Alzheimer's hypotheses here: Hypotheses with greater uncertainty suffer the same treatment, where not having as clear an idea about what it is causes it to be entirely discounted, for years, in favor of the clearer action plan.

jleyank 4y ago

Remember they need new ideas and then they need animal models with which they can test these new ideas. They had one, they had drug candidates that satisfied the model and yet nothing happened. We’ve just seen the various tries run down and smell the smoke of billions of dollars burning to ash. It’s research not engineering and we can’t experiment on people. Huge unmet market need will keep companies trying.

mikenew 4y ago

There's a lot of articles recently on how we're "rethinking" Alzheimer's, and what is utterly baffling to me is the way none of them seem to mention that it has recently come to light that much of the foundational research on Alzheimer's was falsified: https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease https://www.science.org/content/article/potential-fabricatio...

alexfromapex 4y ago
And they mention the “resistance” in the scientific community to consider causes other than amyloids which is introducing human biases into the scientific process
UncombedCoconut 4y ago
Great news: this article does discuss it. It links to that exact Science paper.