Whether it was fraudulent or just incorrect is a different question. We don’t know all of the details of human biology. We don’t even know what all we don’t know. Most guesses work to some degree to keep pharma alive - otherwise nobody would fund the business.
Edit: Google the in the pipeline blog. This and other have discussed this at length.
I thought despite the fraud, it's still the best model we have[1]? The fact there was fraud doesn't mean the model is immediately incorrect. At best, it means its foundations are shakier than we thought, but it's not a slam dunk repudiation.
[1] https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...
The problem us "consensus science". You could get funding to research beta amyloids, but not to research any competing hypotheses.
It's much like climate science today: any dissent at all, even just questioning the predictions of catastrophe, immediately brands you as a heretic.
Nonsense. It is actually quite unlike climate science, where the consensus of catastrophe and the evidence for it are both overwhelming. Dissenters are listened to only to the extent they can provide overwhelming evidence to the contrary, which they so far cannot.
If anyone wants to know who wrote the article linked before wasting time reading it, there you go.
wrt. original post - quickly googled, and that for example https://www.news-medical.net/health/What-are-Amyloid-Plaques... - pretty short and seems to be clear that amyloids do have some correlation while may or may be not the cause.
"Amyloid plaques form one of the two defining features of Alzheimer’s disease, the other being neurofibrillary tangles"
Interesting that the latter is inside the neurons while the former is outside - speaking of complexity. The article also describes that activating microglia back helps with amyloid plaques while this
https://pubmed.ncbi.nlm.nih.gov/33010092/#:~:text=The%20stud...
"The neurofibrillary tangles (NFT) and amyloid-ß plaques (AP) that comprise Alzheimer's disease (AD) neuropathology are associated with neurodegeneration and microglial activation. "
Human body reminds a large monolith codebase - fixing one thing breaks some other :). Claude Code, Human Body CRISPR edition, can't come soon enough...
The current findings seem consistent with "both plaques and tangles are significant components of the pathology" and "our interventions are typically late and the accumulated neurological damage is already extreme by the time clinical symptoms show".
Attacking the plaques wasn't completely worthless - findings show that this often slows disease progression, especially in early cases. There are pre-symptomatic trials ongoing that may clear the air on whether "intervention is late" is the main culprit in treatment underperformance.
> I thought despite the fraud, it's still the best model we have[1]?
It is observed that one of the features of neurodegenerative diseases is decline in glucose metabolism. Supplementing energy availability (e.g. ketones [1], creatine [2]) does improve symptoms in patients with wide variety of CNS diseases, including Alzheimer's, senile dementia, epilepsy, and migraines.
The ATN model you have linked might as well be just ONE OF possible pathways to glucose uptake inhibition, which could be the causal pathology of the symptoms.
So no, it is very much not necessarily the best model we have. Inhibiting any pathway towards a disease is always a good thing, but the characteristics of "best" models are broad applicability and we have a serious contender.
[1]: https://link.springer.com/article/10.1016/j.nurt.2008.05.004 [2]: https://alz-journals.onlinelibrary.wiley.com/doi/full/10.100...
What happened is we got the tools to start studying viral associations with other diseases and ... whooops ... suddenly there are associations. The shingles and RSV vaccines seem to affect dementia while others like influenza don't.
Now people can ask questions about why those particular vaccines affect dementia while others don't. And suddenly we have falsifiable tests.
Now we can subject all hypotheses (including Amyloid) to stronger scrutiny.
The hypothesis didn't come from nowhere.
To contrast, look at how much trouble medicine has had treating brain tumors. It has taken a long time to get effective treatments for various reasons. And Alzheimer's is way less direct in cause/effect.
And before someone says, "well theres nuance to it," "in hindsight its easy," "biology is complex," my answers are, no no and no. Debate me. Ill bring receipts.
as general of a label as it may be?
Somewhat ironic given the context.
To be clearer, Pharma is chasing a nice long treatment plan, that will require expensive drugs till the end. Pharma does not heal - this is not good for business. So there are criteria around what they are searching for.
This is a trope regurgitated by people who don't know any better. It would imply that pharma are deliberately avoiding research directions that would generate cures, or (even worse) discovering cures and putting them in a dark secret safe somewhere.
The reality is that drug development is serendipitous and really hard, and any company seeing even a sniff of a drug that works will throw everything behind making that drug a success. During the early stages of investigation of a promising new agent, the animal data can't predict much, and certainly can't predict whether something is "curative" - this would only be seen during human trials, after which hiding that benefit would be close to impossible. It's just not how it works.
There are plenty of examples of actual (rather than functional) cures being developed and marketed:
1) Previously-untreated DLBCL (a type of blood cancer) can be cured. CHOP chemotherapy cured ~35-40% of cases. The addition of rituximab boosted that to 60-65%. There then followed a long string of failed phase III studies (probably billions spent, cumulatively) trying to beat rituximab + CHOP, and finally in recent years there has been some success. So: multiple attempts across multiple pharma companies, trying to improve on an already impressive cure rate... not much evidence of an anti-cure conspiracy.
2) Hepatitis C - cures were discovered and marketed from ~2014 onwards; now ~95% of cases can be cured with a treatment lasting only a couple of months. So: multiple treatments, from multiple pharma companies, which offer a hugely effective cure for a pretty unpleasant disease.
From the human perspective, researchers are people, and they do have their incentives. Making a breakthrough, of any kind, is important for them - even if for their career (but many do genuinely care and want to help humanity as a whole).
From marketing and sales perspective, look at what happen to pharma companies capitalization when Ozempic appeared: a relatively small Elly Lily suddenly got bigger then Merck, Novartis, Roche or Johnson & Johnson. You can hardly call it a long treatment plan with expensive drugs "till the end".
Really, there is a lot of bad things going on in healthcare and pharma industry, but the conspiracy theory "they don't want to invent efficient drugs" really makes no sense when you dig deeper.
An example of “good” pharma would be Hepatitis C. We can now cure that. Although, pharma is charging the lifetime equivalent in order to do that (a treatment can run over $100k and insurance balks at covering it)
So pharma will absolutely develop a cure if they can. They however will still charge you as if you had to take a dose for the rest of your life.
Lots of treatments start expensive and then come down in cost as competitors step in.
> From the human perspective, researchers are people, and they do have their incentives. Making a breakthrough, of any kind, is important for them - even if for their career (but many do genuinely care and want to help humanity as a whole).
Researchers are people, but they are paid and directed. They can't go off and do what they like. The corporation directs them, and they are paid for their efforts. Researchers (and all working people) aren't doing what is right - they are doing what they are paid to do.
All the financial upside for pharmaceuticals is in prolonged treatments. It is a 'long sickness' industry. This is perhaps too bitter a pill to swallow for most, so this is where marketing and education come in with the sugar.
"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.
It has not worked out that way. Research focused on amyloid, and the development and testing of experimental drugs targeting it, have sucked up billions of dollars in government, foundation, and pharma funding with nothing to show for it. While targeting amyloid may or may not be necessary to treat Alzheimer’s, it is not sufficient, and the additional steps almost certainly include those that were ignored, even censored. Probably the most shattering turn came in March, when Biogen halted the study of what proponents called the most promising Alzheimer’s drug in years — an amyloid-targeting antibody."
I still refer to this article seven years later. Groupthink in the medical research space sets back progress by decades. And it's not just Alzheimers. The FDA's approval process is stymied by a CYA culture that fails to adopt the risk profile it needs to in order to potentially save large contingents of sick and dying.
Except the history of FDA approval here is that it has been too accepting of drug candidates for Alzheimers with very weak evidence of efficacy and serious side effects. This particular field would probably be better off if the FDA took a harder position on efficacy, rather than deferring to drug companies and patient/caregiver groups that desperately want something.
Instead, at the start of a treatment on a patient, an analysis must be done of all available data, and the treatment only allowed if the error bars put it within the realm of the best treatment available.
That means at the start when not much data is available, it is easy to give it to a patient. But over time as more data comes in it gets harder and harder to do so if the treatment is ineffective or harmful.
Data should be collected and analyzed in real-time - it should be a matter of hours between some life event like a death feeding into the dataset used for decisions on new patients.
Biggest example of this risk aversion is the peptide craze going on (the most famous of which are GLP-1 antagonists). It's pretty much a wild west where people read a low-sample animal study, and buy a drug that's "for research only, not for human consumption" off of a compounding pharmacy in China.
Few human studies because even if you have willing and enthusiastic volunteers it's too expensive and creates legal liability. And the FDA cannot approve it without a high bar of evidence (for effective treatment and low risk) and costly, time consuming reviews. Because of this, there is a black market for the things and people are basically being their own test subjects.
Karl Herrup has a terrific book on the topic How Not to Study a Disease — The Story of Alzheimer’s from MIT Press (2021, ISBN 9780262045902). He did not win many friends but I think he is right.
The consensus now is that many factors contribute to the heterogeneous diseases we now call Alzheimer’s.
Fraud is everywhere and we still move forward in most arenas.
People love to praise “the science” when they mean the scientific method. What they always seem to forget is that method is executed by humans. Imperfect, sometimes ego driven humans.
The fact that amyloid-beta binding drugs like Lecanemab and Donanemab decrease progression is also very strong evidence for the amyloid-beta hypothesis.
What seemed to be the hurdle was likely, that targeting amyloid-beta in its pathological form just wasn't easy and developers of pharmaceuticals instead focused (for unknown reasons) on the solid amyloid-beta grains in the brain.
The major reason things are moving so slowly is because of the long development times of pharmaceutical compounds. A new compound will at least have to spend 2-3 years in safety studies before being tested on its first real patient, and then for Alzheimer's, which is a slowly developing disorder, nothing short of a 2-year followup time will show efficacy unless it's truly a miracle compound.
[0] https://www.cochrane.org/evidence/CD016297_are-medicines-ant...
While these two classes of drugs target the same molecule, they are developed to target amyloid-beta in very different forms. Pooling all those drugs together, and then showing very weak effect, makes absolutely zero sense, and I hope and expect this review to be pulled soon.
As to the trials specifically for Lecanemab and Donanemab, the benefits are not claimed to be either strong or large, even by those who support it. The current support these receive is more aligned with the concept that an improved targeting of Aβ amyloid might improve outcomes. This remains to be demonstrated.
It's legimate as people with DS have a hugely increased risk of AD. Their risk increase seems likely related specifically to Amyloid. Many with DS can consent to it.
In general my completely gut feeling is that once we can target Tau we might find that targeting amyloid is needed to fully curtail progression.
Trials are currently ongoing. The results should start trickling out in a few years...
The research is still in the very early stages (largely mouse models, though they did develop the hypothesis by looking at differences in human brain tissue post mortem), but to me my biggest fear is that little research will be done because the "cure" is a commonly available, non-patentable supplement, lithium orotate.
As someone in middle age with a family history of dementia, I've decided to start taking lithium orotate because the risk/reward profile looks so good from my perspective. Lithium orotate has been sold as a supplement for decades, and at those levels it is very safe with extremely-small-to-no chance of adverse effects (e.g. https://www.sciencedirect.com/science/article/pii/S027323002...), so I figure the worst that can happen is I'm wasting my money, but I'd take that for even the small chance that it helps ward off dementia.
Earlier today I read a comment here mentioning Dr Michael Nehls who writes about lithium and also dementia (highly recommend his books). Now that comment is no longer there. Hmmm.
I experiment and take a small number of less-commonly-known supplements and those kind of studies _in itself_ should never contribute to “it’s safe for humans”.
Anecdata: my personal brain/body didn’t react too well to 1mg a day, I felt somewhat ‘sluggish’ and found concentrating harder, so I stopped after 2 days out of being conservative. Perhaps I’d get used to it, but for me personally, I was surprised at the effects of just 1mg so I didn’t want to continue taking it.
Alzheimer's (like a gazillion other diseases) is a product of senescence, and senescence is a subject that faces strong ideological headwinds. That leaves the medical system in a situation where they want to treat the symptoms (the diseases) instead of the root cause, and treating the set of symptoms that we call Alzheimer's is going to be tough.
The insider joke is that the “A” in NIA stands for Alzheimer’s. The deeper and sadder joke: when you fit cognitive trajectories within the subset of people who go on to develop AD, about half of the variance in their test scores is accounted for by chronological age alone.
We’re spending seven times more on the disease than on the clock — and the disease is mostly the aging clock.
Go figure.
NIH is great at tactical research but terrible at strategic research, and politicians do not help much ;-)
Alzheimer's isn't a single-point-of-failure disease, more like a dysregulation of maintenance. So there are lots of things that can tip the odds one way or another, and we may get a lot better at prevention - to the point of reducing incidence maybe five-fold, or delaying its symptomatic onset to beyond the relevant lifespan - but the idea that there might be a single "cure" seems like wishful thinking.
It may also prove to be that, like a spinning-top, once things start to go off-axis it may be very difficult to restore the original stable state, and at most we can just slow it down a bit.
Perhaps more uncomfortable, if most of the effective interventions, risk-reduction-wise, are social/lifestyle related, that has implications for whether people have the agency to access those things.
(Time/energy/facilities/resources for exercise/active lifestyle being an obvious case in point, which is already well known to have a moderate protective effect).
Alzheimer's disease may occur either due to inherited mutations in the genes for APP or presenilin, in which case it can occur as young as 40 yrs old. Or it may occur "sporadically" in those over 65yrs old. The brain pathology of both is similar. Notably, amyloid is derived from APP in part by the action of presenilin, which cuts the APP protein to release the amyloid peptide (Aβ).
Currently, the amyloid hypothesis is the only known way to reconcile the similarity of pathology (for both amyloid and tau) between early onset inherited AD caused by mutations in either APP or presenilin, and later onset sporadic disease. Furthermore, all the mutations in APP that cause Alzheimer's disease are located within or adjacent to the region that corresponds to Aβ amyloid, and not in the remaining 95% of the molecule.
Until another way of unifying these observations is found, the amyloid hypothesis will always find supporters.
For decades, the industry standard was to hunt for targeted small molecules to solve singular biological issues. And to be fair, I don't think this was because of a lack of vision as it was simply the strict limit of our technological capabilities at the time. But attempting to treat a cascading, systemic disease like Alzheimer's with a single targeted molecule is like hoping replacing one pipe will solve the problem when the issue is that the entire plumbing system is corroding.
This fundamental mismatch is exactly why clinical progress has stalled, and I believe the future of treating Alzheimer's will instead closely mirror how our approach to oncology has evolved.
We spent years searching for a universal molecule to cure cancer before we accepted reality. We now know that effective treatment often requires sequencing a tumor's mutanome to develop a highly personalized intervention for the individual. As neurodegenerative systems fail with age, we face that exact same biological complexity. A traditional small molecule is not going to rescue a globally failing network.
My personal take is that we won't see a true breakthrough in Alzheimer's until capital fully rotates out of these legacy, single-target pipelines and into programmable biological systems.
When a topic only has a limited number of experts, those experts become gatekeepers.
Those gatekeepers directly or indirectly control research funding.
Gatekeepers necessarily harbor biases, some right and some wrong, about how the field should progress.
For Alzheimer's, some gatekeepers were conflicted and potentially directed the field in the wrong direction. Only time will reveal AB42's true role.
It's easy to find fault in Alzheimer's.
It's harder to see the general solution to the gatekeeper problem, i.e., how to allocate resources in areas with limited experts.
Perhaps funding like public grants could be controlled by few? Should not the case for private money?
Relatively common health issues older people tend to get fair amount of private funding after all.
Rich people tend to be older and they are lot more likely to see amongst their friends and family Alzheimer's and Parkison's or even cancer and so forth and be worried about it and thus donate money to them.
In somewhat related (i.e. old people health concerns) life extension research gets all kinds of wacky non traditional research lines get funded all the time, I don't understand why would Alzheimer's would be any different.
Generally, you rely on experts.
Who typically became experts by adhering to the conventional wisdom set by gatekeepers.
"Science advances one funeral at a time" feels apt.
Sadly, the problem isn't confined to Alzheimer's.
Whenever only a few people decide what is "right," the same pattern of stifled innovation will generally manifest itself not by design or from malice, but because it's hard for a small group to be 100% right on what works and what doesn't -- especially on matters as inscrutable as neuroimmune diseases.
While there are counter examples and inefficiencies in the system (and there are idea of addressing this, by distributing some part of the money in other ways), we have far bigger societal issues because people do not believe in science, especially where there is an industry lobby sowing doubts.
So I really want to push back against the the idea that the scientific system is broken. While there are real issues, this is still very misleading.
https://www.nature.com/articles/s41586-026-10407-9
(I’m an author)
The takeaway is to stop pretending that we can do good science when the ambiguity is so high, the majority of funding should go to people working on more concrete problems. We never locked in on vacuum tubes because the downsides were so obvious and the upsides of silicon transistors (if they could be made to work) were also obvious even to people outside the field, where your talent comes from. At the very least funders can't allow shifting goalposts, make them up front answer questions about the drugs. That will give you something to estimate the value of the drug and then when they come back with study after study outside the ranges they gave, you lower their funding. E.g. This is supposed to work on someone who was stage 2 and stop progression and then 5 years later it only "works" for stage 1 patients.
Strange breakthrough ideas can't even exist in the current system structurally, so going this route is the only logical choice. Which begs the question, why aren't clinical trials a private venture already? Governments are burning billions of taxpayer dollars for either nothing or cynically to keep the boomers alive and voting even longer, while 1/5 children are obese. For the rest of us we've socialized the risk and privatized the profits.
I like to view degeneration of any tissue as death due to (premature) aging. So, if we treat it, we achieve immortality by applying it to all body. This is something hard.
Alzheimer’s occurs when Amyloid/Tau debris accumulates faster than the glymphatic system can export it.
Parkinson’s occurs when α-synuclein (Lewy Bodies) accumulates because the cellular recycling system (Mitophagy) has failed.
While Choline is a critical bottleneck for Alzheimer's, Glutathione and GBA enzyme activity are the primary bottlenecks for Parkinson’s. But in both cases it depends on the person and their genetics and what matters the most. If someone is at high risk for Alzheimer's a multi-pronged approach will probably be very common. For example a post menopause woman who is not on HRT, but at high risk due to parents should be getting Choline due to the low PEMT expression, but they might have a higher risk for neuroinflammation via NLRP3 and so need to also combat that too.
To say no progress has been made is to ignore the fact that we have learned a ton about the various components of these systems and how they can break down.
Here are the two approximate decay equations that you can put into an online latex viewer.
Alzheimer's
\Psi_{AD} = \int_{0}^{t} \frac{[(\mathbf{K}_{\tau} \otimes \mathbf{K}_{A\beta}) \cdot \mathcal{I}_{NLR P 3}]}{[\mathcal{G}(Li \cdot GSK3\beta^{-1}) \cdot PRO(ER\alpha \cdot \text{PEMT}) ] \cdot \Omega_{ATP}} \cdot e^{\left( \frac{\Gamma_{\text{fibrosis}} \cdot \text{PAI-1}}{EPA \cdot \text{Natto}} \right)} \, dt
Parkinson's
\Psi_{PD} = \int_{0}^{t} \frac{[(\mathbf{K}_{\alpha\text{-syn}} \otimes \mathcal{I}_{LRRK2}) \cdot \mathcal{I}_{NLRP3}]}{[\mathcal{G}(\text{Parkin} \cdot \text{PINK1}) \cdot PRO(\text{Dopamine}_{\text{flux}})] \cdot \Omega_{ATP}} \cdot e^{\left(\frac{\Gamma_{\text{Oxidative}} \cdot \text{Iron}}{\text{Glutathione} \cdot \text{GBA}}\right)} \, dt
And for good measure here is cancer
\Psi_{Onco} = \int_{0}^{t} \frac{[ (\mathbf{M}_{mut} \otimes \mathcal{G}_{growth}) \cdot \mathcal{I}_{STAT3} ]}{ [ \mathcal{G}(p53 \cdot \text{PTEN}) \cdot PRO(\text{Anoikis}) ] \cdot \Omega_{ATP}} \cdot e^{\left( \frac{\Gamma_{hypoxia} \cdot \text{VEGF}}{\text{Repair}_{DNA} \cdot \text{Immune}_{flux}} \right)} \, dt
The point of these isn't to give an exact equation, but to make the understanding of the systems and their components radically simpler for humans to understand which can help with treatment leading to questions like "Where is the bottleneck in this patients system?”
Possibly the most likely possibility?
1. It acts on the brain, one of the organs we understand the least.
2. It's relatively slow acting, and easy to miss in the early stages.
3. It impacts the older population which will have confounding health factors.
4. It doesn't fit neatly into a big category we already know a lot about, like infection or cancer.
The slow acting nature of it means also you have to wait a long time to see results of clinical trials; also because early stages are easy to miss that also means you are stuck studying people who are already pretty senile and thus might be beyond the point where you can make a big difference.
Ruxandra has a nice piece, focused on cancer, but the reasoning is basically the same here: biology is just really hard. Sometimes we get lucky but in general it's a long, slow slog.
[1] https://www.writingruxandrabio.com/p/why-havent-biologists-c...
Think of it like brushfire in an ecosystem, or species population imbalances leading to catastrophic breakdown. These are better understood in terms of system state and preconditions, as opposed to a trigger event.
Infectious disease, at least in the classic acute form (whether that's bacterial and fast - cholera - or viral and slow - HIV), is a more mechanistic process which can be halted by blocking a single step in its pathway.
Systems that remain healthy and balanced via dynamic processes are harder to reason about and fix, because the root cause of a disease state can be dozens of little things adding up to the system losing its ability to maintain homeostasis.
I'm dealing with someone with this disease now and it's absolutely hell.
Scientist Ruth Itzhaki spent years studying a far more promising theory of Alzheimer's: that it's caused by viral infection in the brain, particularly HSV-1, best known for causing cold sores. Most have it, so there are clearly other factors at work, likely related to susceptibility in particular individuals to to the virus infecting the brain and spreading over time. See https://pubmed.ncbi.nlm.nih.gov/34205498/
The implication is that anti-viral treatments are likely to inhibit and potentially cure Alzheimer's. There is already unintended evidence along these lines, both via antiviral drugs and vaccines.
If you're looking to beat type-3 diabetes, you need to have a daily routine of exercise while you're young to keep these systems in shape when you're old.
You also don't need to belong to any marginalized groups, as ACEs tend to wear your body out over time -- breathing, kidneys, and heart in particular. People with traumatic childhoods (bullying, abusive parents, etc) have a huge risk of dying of dementia -- if their kidneys don't give out first.
Well, they seem to have some champions here...
I think you’re making a giant leap from A to Z and missing a whole bunch in between.
Stress ages the body. Homeless people can age several years, being on the streets for just a few months.
I've also seen numerous people in these upbringings die in their 50s and 60s from kidney failure. My stepdad was one of them. My father too.
My father had a normal childhood, except he had a traumatic experience of shooting his twin brother while they were playing cowboys and indians. Spent his entire life blaming himself. Went through all the normal development phases. Not on any meds.
His body just started shutting down prematurely. It's common in people with those experiences. First, his breathing got bad. Then his kidneys. Then he started having heart problems.
And that's the pattern. Heart, lungs, kidneys. Which are all linked to the brain. And eventually lead to dementia-like symptoms. At least that's what the research on ACEs seems to point out.
Marginalized people have a high death rate in their 50s and 60s, because of societal bullshit -- no other factors needed.
which is linked to nervous and endocrine dysfunction,
which is linked to Alzheimer’s/Dementia?
Meaning, failing of the glymphatic (and possibly lymphatic!) systems.
I'm pretty adamant it was fraud. You don't have to look very hard to see how profit incentives are fucking up the health/medical sector. Check out how often $1000+/dose drug goes generic and within +/- 3 months a study is published that reveals it can be strongly linked to any number of issues that would have caused it to never get approved in the first place. Then you look at the original studies and see they specifically excluded anyone that those problems would have shown up in!
Alzheimer is very important, and affects a very large number of people, it is getting lots of research funding and attention, but perhaps not enough? If it takes a certain combination of time, human-hours, money, and lots of smart people being interested in doing research in that field. Is the economics of disease research that simple? it is unknown what numeration of those variables is required to tackle Alzheimers, but if it is a lot more than cancer for example, then it might be decades or more away from being well understood.
I hate to say it, but cancer and HIV feel more like things we can get, Alzheimers feels like something only old people get, and it's to easy to forget that we'll get old, and it's hard to think our older loved ones might be affected. If no one in your sphere has been affected, it's harder to prioritize the disease.
My opinion is, money is the biggest obstacle, and I don't mean money for research, but money for education for researchers, and the talent pipeline. If higher education (at least for medicine) was literally free, that'd be a start. then you need lots of people getting paid to do the research independently. Right now, it feels like most disease research is being done by big pharma, so they can find the next insulin they can use to maximize profits. The incentives are all wrong on all sides, for potential researchers, the public and R&D companies.
https://en.wikipedia.org/wiki/Early-onset_Alzheimer%27s_dise...
Depending on what you consider "old", this might not change much
> and it's hard to think our older loved ones might be affected
A large proportion of people don’t need to think about it because they have witnessed the horrific effects on loved ones first hand.
Unfortunately that insight hasn't led closer to a cure.
It also turns out sort of bad to tell people they have a horrible neurodegenerative disease 10 years before the major symptoms start.
Why isn't everyone's mind blown? Well for the cynical explanation, look at the state of science education and what people said about Artemis, vaccines, etc. or optimistically, there are too many mind blowing discoveries to treat them all fairly.
https://www.bellyofthebeastcuba.com/us-citizens-in-cuba-for-...
https://venezuelanalysis.com/news/us-hardens-sanctions-targe...
We were introduced to the head of neuroscience at Houston Methodist as part of our due diligence process; his entire career was built upon the removal of plaque from the brain and would not even consider an alternative theory. We ran into this for years. It made funding the trials very difficult. We were totally ignored by all the Alzheimer's charities and orgs (ie Seth Rogan's for example). Only the Michael J. Fox foundation contributed early on.
However, our drug, now known as Zunveyl, was a pro-drug of already on the market Galanatmine, which was the second most commonly prescribed drug in the world for this disease (about $6BN/yr). Our pro-drug almost eliminated the side effects of Galanamine (nausea, vomiting) and enabled us to increase dosage high enough to actually get enough molecules into the brain. It was (is) awesome. Some of our first clinical trials were healthy young adults - they did extremely well. I don't think I can share the actual results but I hope that we (or someone) can fund a study to get approval for "regular people" usage one day given how well this test went. Later tests went just a well but only thanks to the "fast track" program were we able to even get to market.
Even today after being on the market for about a year now, the market uptake is slow due to insurance company approvals. We are getting reorders like crazy but often new patients get denied initially and then doctors have to appeal and then they get approved. This has been taking about 6 months on average and is brutal for people with the disease (and their families). Since getting a drug to patients is actually a (sadly and surprisingly) large sales and marketing expense, the company (Alpha Cognition) is focusing on long-term-care centers for now, but we had always hoped that this would be available much more broadly and much faster. Several of the early investor's parents were alive and afflicted with this disease when we started, but have since passed away. I hope that we can get this out and help others - faster.
The mother company that spun this out is also working on other molecules to try to stop Alzheimer's itself, rather than "only" help with symptoms but as always funding is a challenge. Clinical trials must be done correctly and are thus expensive.
Been living this battle for 15+ years and hoped that this can shed a little light on how things have been.
Next question.
But fair, improved biomarker data does not mean the drug is making any real improvements for the patients especially with the side effects. But it is also well known.
https://www.scientificamerican.com/article/amateur-armed-wit...
Just like that math problem, we are starting off with wrong thinking right from the beginning. Some researchers are already talking about this but the plaques are actually a protective response to a metabolic problem in the brain which has to do with glucose transport.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8772148/
This is why people with dementia and Alzheimer's crave sweets so much:
https://helpdementia.com/why-dementia-patients-crave-sweets-...
Alzheimer's is not a neurological problem, it is a metabolic problem.
That's also why Alzheimer's can take so long to develop. It's just one aspect that we've chosen to focus on because it's more clearly noticeable, but it cannot easily be treated in isolation from everything else. If it was, it would regress quickly without fixing the root causes.
Even the most unwell person (in the US) is still dragging themselves to the store and work, on average.
Simple, brief movement that we often relieve the elderly of is the pump that actions the lymphatic system.
Being older brings its own additions to the table.
The President is singlehandedly kept this side of functional via infusions of this drug each month
https://beingpatient.com/fda-alzheimers-leqembi-nih-memo-tru...
They mysteriously rushed approval despite all other activity suspended the week after he was sworn-in
Watch how he disappears for a few days each month, that's why, it can only be done in a hospital and they have to do MRI for leakage
If you study effects and not causes due to lack of measurements for reproducibility in any field of research, that's what comes out.
Also check out how the new and promising correlation started by observing the Wales eligibility for mandatory shingles vaccination during an outbreak and the effect on that test group when it comes to alzheimer or dementia in their old age.
Note that shingles (herpes zoster) virus is a dormant virus for decades, and it's not really treated because of that.
Also note that this was only discovered because people died and their data set was publicized because of that, which I hope that can happen in an anonymous way due to it being invaluable for medical research.
[1] https://www.alzheimer-europe.org/news/analysis-electronic-he...
[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC11485228/
[3] https://www.sciencedirect.com/science/article/pii/S009286742...
[4] https://www.alzforum.org/news/research-news/shingles-vaccine...
Or maybe virus activity is one way that a negative feedback loop involving protein aggregates can begin...
A lot of virological and parasitical components have historically been wrongly associated with genetic markers, too. Toxoplasmosis parasite comes to mind.
Alzheimer's is basically an advanced form of gum disease caused by Porphyromonas gingivalis) that has infiltrated into your jaw and then traveled into your brain where it causes systemic inflammation which in turn lets other pathogens in that cause neurodegeneration.
There is probably no cure because the only thing you can do in dentistry is prevention and preventative dentistry is still in its infancy.
This is probably wasted on the HN crowd though, because I haven't seen any demand for preventing Alzheimer's.
About the question: Alzheimer’s disease is a condition of the elderly, and they’re on their way out anyway. That is what I observe. Healthcare is a moneymaking business. In capitalism. While it should be free. And excluded from patenting or copyrighting. Healthcare has turned into wealthcare. No wealth? Game over. No extra life for you. On the other hand, maybe the subject is just so complicated for today’s scientists. It is all in the eye of the beholder. The existence of F1 racing cars doesn’t mean that Tesla will never be part of Formula One’s future. As we speak there’s already one Tesla racing through space…
Disclaimer : I work as the CTO at BetterBrain
[0] https://www.thelancet.com/commissions-do/dementia-prevention...
Protective against the problem is anything which keeps you mentally active, such as socialization, work, religious community participation, hobbies, and meditation. Retirement, death of partner, isolation, sleep deprivation, depression, dissociation, psychosis, medications/drugs which interfere with restful sleep increase risk.
A possible falsification of this hypothesis would be if it's caused by inactivity or physical self neglect, as those often go hand in hand with the correlated and anti-correlated factors mentioned above.
This is particularly interesting:
> Intriguingly, studies show conscientiousness and neuroticism to be associated with Alzheimer’s disease and related dementias but not with their pathologic hallmarks such as plaques, tangles, infarcts or Lewy bodies in the brain.
Except early onset Alzheimers happens and it also happens to plenty of people for which none of those are true.
The research went awry in Alziemer's due to fraud but its being funded at a reasonable level, a level many with Long Covid or ME/CFS or Fibromylgia would be very happy to see but doubt will ever happen. Funding of diseases is not "fair", it isn't based on number of sufferers * quality life years lost and we should be spending more on medical research generally. Alzeimers is one of the better funded diseases in the world.
I'll probably be downvoted for this, but I honestly think quality of life of CFS is lower than Alzheimer's.
I truly wish that disease funding was based on science and metrics rather than marketing and vibes.
That being said, Alzheimer's absolutely deserves it's funding and it is very sad to see setbacks related to fraud.
Naturally, the far more terrifying and inexorable disease that is incurable and robs people of their entire personality and will affect most of us to some extent (dementia, if not Alzheimer's specifically) by the end of our lives gets more funding and attention, as it should. The way Alzheimer's has been researched and funded is diabolical, though, but you might pick any other of 200 serious progressive neurological disorders that are underfunded and underrepresented over... CFS. CFS isn't even fully accepted as a syndrome at this point - long COVID is probably more accepted as a real thing by practitioners at this point than CFS.
Isn't long covid just CFS that can be attributed to Covid?
If you accept that multiple viruses can cause "long <virus>" syndromes, of which long covid is just one example, it's plausible that CFS is really a cluster of syndromes, one category of which is these post viral syndromes. We just can't pinpoint the virus behind it every time because most viruses haven't been studied as much as Covid has.
