The editors cut my favorite tangent on western blot antibodies, so I insist we put it here. For a western blot to work, you need to have an antibody that recognizes your protein of interest, so it will only bind to the parts of the membrane that have your protein. Typically you make this by exposing something like a rabbit or a goat to your protein, and then collecting the antibodies that it makes. Seriously. Next, you want a secondary antibody attached to a fluorescent marker that recognizes your primary antibody, and usually you just use something specific: often there are tubes called anti-rabbit and anti-goat in a lab. The things you find in a lab. Almost every molecular biology lab has an ancient vial of salmon sperm too, but that’s for another video.
Lol in the same vein as this comment, a video about all the things in the lab that basically amount to real life alchemy and witchcraft would be pretty entertaining
Pffft, if the editor had kept that in the video couldve been over the 10 minute mark! Then again, I guess that shows the seriousness of the editor that they would sacrifice the 10 minute mark for what they feel works best for the video...
Yeah, cuz a statement is a stronger title than a question, but a question of a positive assertion is stronger than a negative assertion because we already know most things aren't true. E.g. People would click on "Monkeys ride motorcycles", but you can't put that if it's not true. No one would click on an article that's titled "Monkeys can't ride motorcycles", so you phrase it as a question: "Can Monkeys ride motorcycles?" You could put the negative assertion if there was an assumption that they should be able to, but were denied the ability as that triggers indignation. That said, if the title sounds dumb or common sense, people aren't going to care to read something they thing they already know.
I don't have any family history of Alzheimer's disease, but I'm at the age where every time I have a 'senior moment' of temporary memory loss, I think about this. To me this would be the worst kind of end of life imaginable.
Man, that is gonna TERRIFY me when I get a bit older. I am already prone to worry so the first time I start getting serious brain farts I am gonna panic about it being some form of dementia. I agree with you, nothing compares to losing your mind. And I say that as someone who, even in my thirties, has a fucked up body that is disabled from multiple autoimmune diseases and has had a surprisingly amount of my insides taken out or messed with. And has had enough CT scans that they could set the next Fallout in my abdomen. Having other health issues does suck, but I still fear losing mental acuity far, far more.
Forgetting things might well be normal. If you forget where you put your keys, or where you parked the car, that might be fine. Just getting old. If you forget that you have a car, or you start putting your keys in the fridge, or start doing strange things, than that is more indicative of a problem.
I watched the Tiktok video where man said that he constantly would lose his train of thought during conversation and would just blank apparently this man was having focal seizures maybe that's what you're having having too as a senior
This is one of the most cruelest disease. I'm seeing my Dad go through it and it's the hardest thing I've had to deal with in my life. Even harder than heartbreak. I'm so glad scientists are making an effort to get to the bottom of it. I hope one day people can get meaningful therepy to reverse it or at least stop progression to a certain point.
I'm so sorry your family is going through this. The experience can be so painful, for both people with Alzheimer's and for everyone who cares for them. Thank you for sharing this, it's a good reminder that this is not a purely academic exercise. Wishing your family well.
@@SixOhFiveI wonder how someone can have the most cruelest response to a person relaying the horrible time they're going through by being a grammar fascist. If you can understand the meaning behind the message, it wasn't incorrect. That's how language works. If you aren't going to figure out and use the exact grammar and syntax of P.I.E., you don't get to claim any kind of correctness. And even then you'd be incorrect because language changes.
Thank you so much for making this video, when the whole thing first blew up I remember having hours long conversations with close friends about what it means and how dramatic the articles I kept seeing were. And then, just silence on this, I've not seen any major news ors follow-ups to this other than the recent retraction and it's made me sooo confused about what was happening in alzheimer's research. It's incredibly reassuring to see this be a shared sentiment and for someone with the actual resources to go through in figuring it out, things look sensible again now.
There's still some major issues with the studies of those anti-amyloid mAbs and the drugs themselves. Supposedly slows progression but the effect size is tiny, plus ARIA (brain oedema and microbleeds) is a huge issue. As a geriatrician neither me nor my colleagues are particularly excited about them. The best evidence we have so far is for cardiovascular risk prevention/reduction, staying active and having a good diet. It's possible and likely that amyloid is only one part of a pathway that also includes cerebrovascular disease and inflammation - trials ongoing. Is amyloid initially a bystander that then causes a lot of harm? Quite possibly. Amyloid angiopathy for example in the brain is a disease that causes vascular dementia through numerous microbleeds and tiny infarcts due to amyloid beta deposition in vessel walls.
When your doctor’s only advice is exercise and diet and you’ve repeatedly told them you do exercise, it’s quite obvious they have no financial incentive to help you. Take note of this, please. Exercise is good but “a lack of exercise” is unlikely to explain your problems. An autoimmune disease is far more likely.
2nd point: humans are still confusing correlation with causation. We know acne stops when people come out of puberty. But for some reason no one decided to test for this when testing synthetic vitamin a (retinols / accutane). They invented a drug that stunts growth, not one that cures acne.
@@user-zu1ix3yq2w thankfully there's active research into anti-inflammatory medications for Alzheimer's too, so we hope that that will help. Same with how medications can help with cardiovascular risk factors. We're still a long way to really understanding a lot of things in neurology to be honest. A lack of exercise or "the wrong diet" is definitely not the reason for most medical issues , even if exercise and diet change can help people, it's a kind of treatment. Even then, exercise and diet does not help everything.
A few months ago, I did a presentation on the two drugs I assume you were referring to (Leqembi and Aduhelm). I was pretty disappointed in a meta analysis's (Ebell, Mark H. et al) results about multiple anti-amyloid MABs' effectiveness. There were statistically significant results but not much in the way of what most would consider clinically significant.
"fancy scanner" and "image duplicatioin" instanly makes me recall the xerox scanner compresion scandal, where the scanner wanted so bad to compres that it changed data. The famous examoples were changing 6-8-9 around, 3 to 5, etc. on invoices. Are we sure that did not happen here?
Oh yeah, absolutely. This was also my first thought hearing about multiple other allegedly falsified studies with suspicious data - because that data oftentimes was in images, which looked like they may have been scanned.
Nice comprehensive, yet brief, video on the subject without resorting to "baby language" and losing the science. A great job at balancing all of these conflicting interests! A truly wonderful example of Science Education that's informative without being either impenetrable or meaningless. Thank you!
One of my favorite pieces of research relates to the correlation, seemingly causitive, between HSV/shingles and AD. When you said "culprits or cooccurrences" - that is a MASSIVE difference here. The viral origin hypothesis has some of the best data I've seen as a scientist behind it, although it is limited in total quantity for obvious reasons. The cool part about that is that it provides a treatment as well - we discovered the cause by accidently treating the disease with antivirals (as in the Japanese studies), or with a vaccine (as in the welsh shingles role out).
Even if amyloid plaques cause the onset of symptoms, it still doesn't make for a cure until we figure out why the plaques are forming in the first place. I mean, it’s a start, but it’s just chasing symptoms at that point.
It is inflamation causing dysfunction like many many other neurological and psychiatric issues. Diet,blood sugar control and antiinflamatory suplementations are way effective at treating them because of it. Brain seriously cant take chronic inflamation. Some neurons are especially susceptible like dopamine.
@@exosproudmamabear558 That wasn’t my point. Treatment of symptoms is not a cure. It's like a headache; you can take medication for it but that doesn't solve the reason you have a headache and headaches are a response to a vast number of issues, some of which can lead to death.
@@jmi967 I know and thats why I told you the main reason but intermediate parts are missing of course which will be used in real treatment after all inflamation has different pathways and they need to find which pathway they neednto specifically target. But instead they are trying to get rid of plaques. Typical medical stuff tho most of the times doctors focus on increasing quality of patients life by managing symptoms instead of just curing it and that leads to worse quality of life. I think the main reason they act like this is because most doctors do not know enough neurophysiology and even the ones research properly are limited since we dont know enough as humanity. Immun system and brain is a mystery when both those things involve everyone starts to blank amd focus on symptoms.
Don't dismiss curing symptoms when the symptoms are the actual problem that needs to be solved. If someone technically has Alzheimers but their cognition is unimpaired… that's not merely a start! So the question is, "how much of the effect does clearing this away actually prevent?"
It's not even an interesting hypothesis, since it does not explain what causes the plaques to form in the first place. Equivalent to the hypothesis "tumors cause cancer".
It’s pretty heartbreaking. How many barely effective drugs targeting protein buildup will it take before the field truly pivots? It should be abundantly clear by now that Alzheimer’s mice are bad models for the disease in humans, likely because they are just mimicking the protein buildup symptom, not the unknown cause.
Hope there is progress. Watching and caring for my mom going through this is torture. The drugs they gave her made her wake up screaming every night and feel nauseous every morning. They switched them up but it had no effect whatsoever.
I am currently an aging researcher, and was, prior to this, an Alzheimer's researcher. One of my earliest mentors was an old-school physiologist from UI Urbana-Champagne (this was thirty years ago). He told me that he and his colleagues used to play a game: they would publish papers and, between them, see who could include the oldest *relevant* reference in the reference section. It's a habit I'd taken on and one that has the added effect of requiring you to follow the successive chain of references down to their source. Think of the game "telephone" where one participant whispers a message in the ear of the participant next to him, until the original message has been misunderstood and taken out of context enough times as to have no bearing whatsoever on the original. In truth, we have no idea what causes Alzheimer's disease. The best analogy I can make for the amyloid and tau hypotheses is an undergrad college party. The morning after, the house is in disarray and everything is out of place. Empty beer bottles and cigarette butts are strewn about everywhere. Naturally, the correct conclusion is to blame the party on the empty beer bottles. Or the cigarette butts. Perhaps the beer bottles "caused" the cigarette butts! Perhaps if we selectively remove the beer bottles and cigarette butts, the house will be restored to its condition prior to the party. Abandoning the analogy, what is clear is that *something* has gone wrong in the brain, and it culminates in a condition called Alzheimer's disease which has some histopathological correlates to plaques of amyloid and tangles of tau. Yet drugging either will have no effect because the appearance of both represents a near end-point in a series of (by now, irreversible) events culminating in the pathology we are familiar with. The field is hopelessly addicted to these two hypotheses and generations of career researchers have lain the tracks on which this train rides to nowhere.
The State Board was meeting in front of the pharmacy school when a professor's name came up for reprimand. The crowd made some noise when the name came up for falsifying data. They changed jobs. But it was seen as obvious when the published data was too clean and not reproducible. There are.conflicts of interest in many medical journals and the damage it does is huge when nobody carches it. Sometimes the same effect can happen by selectively publishing only certain resorts or other.biased studies. So many problems get through. Watch out when they change anything.
We've known this a long time about Alzheimer's. Also removing these proteins will not solve the issue. the problem is WHY the body is putting proteins there, it doesn't do things without a reason. It likely has everything to do with crappy diets and environmental pathogens causing chronic inflammation, the waste from the healing process builds up everywhere causing issues. This is sort of like saying you can cure infections by treating the fever, no you dont.
The treatments remind me of how we handle atherosclerosis. Lower the LDL to stop plaques from clogging arteries without locating and treating arterial hardening in the first place which risks a host of other issues.
A sober explanation, although often flying above my head I got the gist of it. In my world it reminds me of water injection to enhance ICE performance. Just because it works is no reason to pour a litre of water into your cars fuel tank then fake a dynamometer record. Anyone else doing it would at worst destroy their engine at best have it running rough. None of which takes away the undisputable fact that water injection works.
When I hear about Alzheimer’s and dementia I always think about childhood dementias like sanfilipo. Children with dementia 💔 Such heartbreaking diseases.
The evidence for retraction was that the little blobs looked too similar? Are they going based on the original sampli, on the original data, or on the published data? There's like so many computer reasons that picture could be messed up, and even more human error reasons. I mean they don't even like to retract with admission of fraud so i'd be interested in how well they actually traced down the issue with the data, wouldn't the original samples be floating around or do they degrade or get destroyed?
How fraud might guide the direction of research (in terms of what gets published and what gets funded) is sadly not that surprising given publication bias. Scientific journals can be too conservative and can take a while before accepting new measurements. A semi-recent example is the so-called “proton radius puzzle.”
Rather than treating the amaloid after it occurs why not try to find what's causing it and treat that? Probably because we don't know the cause... Let's find out. If we can prevent the amaloid build up then we will either solve the problem or learn they are not the problem (nor is their immediate cause.)
Whatever the outcome a study is not a waste of time until it becomes fraudulent. If experiments give a negative, say unexpected, result, then you have learned something. It is not a failure unless you screw up the process.
Reasonable summary but concluding that Amyloid beta is still a good potential explanation is a very iffy place to leave things. Every anti-amyloid treatment since bapinezumab a decade ago has failed to cure the disease or even to make a difference in the progression. Your buddy Claire has it right when she mentions trying to come up with a more complete mouse model because the mouse models have also lead down dead ends when they aren't similar enough to the cascade of causes and effects in the human pathology.
wait till you understand that the pharmaceutical industry don't want to find cheap and effective cures but profitable remediation that are taken chronically.
Totally random: Is there anyway that the similar mechanisms that occur due to Prion Exposure..?? Maybe there are different types of misfolded proteins that maybe.. could cause a slow chain effect that triggers the Plaque or Taou build up over a long period of time??
Even if americans are more prone to alzhemiers, Correlation does not equal Causation that is a basic rule in statistics It can be a stepping point to figuring out why americans (if they are more prone) are to alzheimers compared to other countries. But just because something is correlated to another does not mean that it is the cause. It can't even be called evidence to that conclusion either because of how many different factors other than diets people face in different regions and climates alongside population density and way more variables
I don't understand why these "alleged" frauds remain "alleged" for so long. Shouldn't we have some clear prove by now? Either by reproducing the study or whoever done the study can redo these tests maybe with an independent observer. Also isn't it odd that some other markers look like duplicates as well?
"Allegedly" simply means "claimed" or "believed". That's different from "proven to have been done intentionally". The paper was clearly bad and should never have been published, but that's a bit different from "I can prove in court that he made a bad paper intentionally", and without that second part, you're likely to get sued for it
I think instances like this highlight the importance of 'AI scientist' in their ability to simply work without trying to meet deadlines or appeal to donors. Surely they'd still be corrupted by their humans but it would take a significant workload off the shoulders of scientists under tremendous pressure to produce results. Where they could simply had the AI tell the shareholder no with significant amounts of data that lead to what the scientist may feel. Cus u know it they felt this science in their bones that is why they lied.
Maybe a diabetes medication that crosses the blood brain barrier could help, diabetes can cause a limb to die because of poor blood flow and infection, and a connection between the two seems to be forming from what I've heard. I've heard somewhere that those amyloid beta clots could be the brains self defense mechanism or (own theory), it could be equitable to scarring. Hope this could be useful.
True. Some researchers believe the microglia have a key role in Alzheimer. And that the plaques cause some immune reaction that worsens the progression. There are also similar mechanisms found with other plaques in the brain
How are amyloid beta and tau proteins hypothesized to cause or contribute to Alzheimer's? I have a superficial understanding of the topic but would like to learn more.
Is nobody going to talk about that microscope?!?! is that what I think it is??? I don't even want to get into how expensive that equipment it is but as the technology gets better it'll get cheaper. I am really excited where my cross copy is going😊
There is exiting research going on however this approach is still medicalizing the treatment of symptoms. Not addressing the causes which is why slowing the progression a bit is all a drug will ever do. It is also wrong to say there are no better alternatives. Professor Robert Lustig has patients cured of Alzheimer's disease, and free of symptoms for over 8 years now when caught early enough. This is by remediating each known cause of inflammation. Mostly it's food, and environment. Everything we normally do wrong. Drug research is helpful in highlighting that only lifestyle well help.
No one is using crispr in the brain because it is considered too dangerous. Crispr still has its flaws of cutting in other places and adding more mutations than wanted. It would be interesting to see if someone did this in mice or cell culture though
I had a large volume of data collection of 10 years worth hacked from my computer for past 20 years.. im doing work on qiantum consciousness and AI and alzheimers cptsd.
We do know what causes it. All vasular dementias are a spectrum of overactivation of the integrated stress response. APOE4 isn't a causal factor. It just speeds it up by supplying more cholesterol to the brain, which is linked to higher IQ in those possessing that variant. Which also causes junk to accumulate if cellular waste management, repair, and nutrient sensing arent working appropriately. May want to look at a gene called MOF, which regulates epigenetic quality control in the brain. Nutrient sensing. Plus, EIF2A and EIF2B, which regulate protein production quality control.
60 Minutes recently posted a video covering a new potential Alzheimer's treatment using ultrasound. ruclips.net/video/3EfX25igUbc/видео.html It would be awesome if there's actually a potential non-invasive non-drug treatment for this disease, which causes so much suffering to patients and families.
Hey, if your lab will do the "uncomfortable, invasive" test for free, I'll volunteer right now! ( I have that mild genetic tendency, so why not?) PS: Western blot? Been there, done that, borreliosiis. Hey, have you noticed increased tendency of dementia with Lyme disease? Probably....Cheers...
There was a clip I watched few months ago, a researcher used red light therapy to treat the brain diseases, a person with Parkinson used this method for 40 days with significant improvement. There are products in the market.
Maybe it's type III diabetes as some suggest. Care home residents in Mesa AZ were put on a strict carnivore diet, many of them had dememtia. Their children were warned, no donuts, no cookies, no candy, no carbs. Several of the residents regained their cognition, some went home to live a normal life.
Did the researchers know that the blot was bad data? if so then there was no fraud. It would only be fraud if they knowingly published bad information. They could actually sue you for defamation for your use of the word.
Because academic publishing fell the whims of capitalist logic years ago. Nature only has to "peer review"(have other scientists actually review stuff for free) a certain percentage of their articles. Just enough for them to keep the prestigious title.
Nature definitely peer reviews its articles, but the image analysis required to spot this is probably not in the wheelhouse of peer reviewers (they'd be Alzheimer's experts, after all) and peer review is meant to look for errors and oversights, not outright fraud. This case certainly shows some vulnerability in the system, but the fact that it eventually got caught is also probably a good sign.
Reviewers are not supposed to be fraud investigators, but to evaluate if the paper is scientifically sound. The reviewer expects that the author is being honest in their reporting, and no reviewer has time to do a pixel by pixel analysis of a western blot.
you say "we don't 100% know" -- the correct phrase there is probably "we probably don't even 50% know". "we're still a little bit in the dark here" 😂 no, you're "mostly in the dark here". this is a pernicious and common problem in science communication. you cannot recognize or accurately quantify how little is known. you repeatedly misrepresent the state of knowledge in casual speech. and specialists constantly do this in technical works. the tendency is to say "just a little bit is left to understand!" when this is false. "it's not like our current best bet therapies are homeruns either" -- again, NO. they are barely BASE HITS. they are barely 25% of the way to the goal. 😂 madness. hubris. exaggeration.
The editors cut my favorite tangent on western blot antibodies, so I insist we put it here. For a western blot to work, you need to have an antibody that recognizes your protein of interest, so it will only bind to the parts of the membrane that have your protein. Typically you make this by exposing something like a rabbit or a goat to your protein, and then collecting the antibodies that it makes. Seriously. Next, you want a secondary antibody attached to a fluorescent marker that recognizes your primary antibody, and usually you just use something specific: often there are tubes called anti-rabbit and anti-goat in a lab. The things you find in a lab. Almost every molecular biology lab has an ancient vial of salmon sperm too, but that’s for another video.
Ugh editors are the worst
Lol in the same vein as this comment, a video about all the things in the lab that basically amount to real life alchemy and witchcraft would be pretty entertaining
Pffft, if the editor had kept that in the video couldve been over the 10 minute mark! Then again, I guess that shows the seriousness of the editor that they would sacrifice the 10 minute mark for what they feel works best for the video...
If you ever want to buy guinea pig blood, yup, lab supply companies. Such as Lampire Biologicals. (NOT vampire.)
Omg I read Freud not fraud and I was like "oh gods not thia a-hole again"
Betteridge's law of headlines is an adage that states: "Any headline that ends in a question mark can be answered by the word no."
Yeah, cuz a statement is a stronger title than a question, but a question of a positive assertion is stronger than a negative assertion because we already know most things aren't true.
E.g. People would click on "Monkeys ride motorcycles", but you can't put that if it's not true. No one would click on an article that's titled "Monkeys can't ride motorcycles", so you phrase it as a question: "Can Monkeys ride motorcycles?"
You could put the negative assertion if there was an assumption that they should be able to, but were denied the ability as that triggers indignation. That said, if the title sounds dumb or common sense, people aren't going to care to read something they thing they already know.
I realized this a few weeks ago,
And i am seeing john's "Is Google Training AI on RUclips Videos?" As next recommentation, which big red yes in the thumbail
Unfortunately not a law. I count when I encounter it, and recently the fraction of "yes" is going up. About 7:3 overall, atm.
@@testboga5991 a law doesn't need to be universally true to be a law, namely because there are multiple definitions of the word law.
I don't have any family history of Alzheimer's disease, but I'm at the age where every time I have a 'senior moment' of temporary memory loss, I think about this. To me this would be the worst kind of end of life imaginable.
Man, that is gonna TERRIFY me when I get a bit older. I am already prone to worry so the first time I start getting serious brain farts I am gonna panic about it being some form of dementia. I agree with you, nothing compares to losing your mind. And I say that as someone who, even in my thirties, has a fucked up body that is disabled from multiple autoimmune diseases and has had a surprisingly amount of my insides taken out or messed with. And has had enough CT scans that they could set the next Fallout in my abdomen. Having other health issues does suck, but I still fear losing mental acuity far, far more.
Well, it might be hard on your caregivers but you might enjoy aspects of it.
Forgetting things might well be normal. If you forget where you put your keys, or where you parked the car, that might be fine. Just getting old.
If you forget that you have a car, or you start putting your keys in the fridge, or start doing strange things, than that is more indicative of a problem.
It is only horrible for you when you remember that you're forgetting. That eventually stops.
I watched the Tiktok video where man said that he constantly would lose his train of thought during conversation and would just blank apparently this man was having focal seizures maybe that's what you're having having too as a senior
This is one of the most cruelest disease. I'm seeing my Dad go through it and it's the hardest thing I've had to deal with in my life. Even harder than heartbreak.
I'm so glad scientists are making an effort to get to the bottom of it. I hope one day people can get meaningful therepy to reverse it or at least stop progression to a certain point.
I'm so sorry your family is going through this. The experience can be so painful, for both people with Alzheimer's and for everyone who cares for them. Thank you for sharing this, it's a good reminder that this is not a purely academic exercise. Wishing your family well.
Sorry but most cruelest is bad grammar, that’s like says most most cruel, by saying cruelest you are already implying it is the most cruel.
@@SixOhFivethank fucking god for Giga Chad correcting their grammar.
@@SixOhFiveI wonder how someone can have the most cruelest response to a person relaying the horrible time they're going through by being a grammar fascist.
If you can understand the meaning behind the message, it wasn't incorrect. That's how language works. If you aren't going to figure out and use the exact grammar and syntax of P.I.E., you don't get to claim any kind of correctness. And even then you'd be incorrect because language changes.
Thank you so much for making this video, when the whole thing first blew up I remember having hours long conversations with close friends about what it means and how dramatic the articles I kept seeing were. And then, just silence on this, I've not seen any major news ors follow-ups to this other than the recent retraction and it's made me sooo confused about what was happening in alzheimer's research.
It's incredibly reassuring to see this be a shared sentiment and for someone with the actual resources to go through in figuring it out, things look sensible again now.
There's still some major issues with the studies of those anti-amyloid mAbs and the drugs themselves. Supposedly slows progression but the effect size is tiny, plus ARIA (brain oedema and microbleeds) is a huge issue. As a geriatrician neither me nor my colleagues are particularly excited about them. The best evidence we have so far is for cardiovascular risk prevention/reduction, staying active and having a good diet. It's possible and likely that amyloid is only one part of a pathway that also includes cerebrovascular disease and inflammation - trials ongoing. Is amyloid initially a bystander that then causes a lot of harm? Quite possibly. Amyloid angiopathy for example in the brain is a disease that causes vascular dementia through numerous microbleeds and tiny infarcts due to amyloid beta deposition in vessel walls.
Yes, I was making the same comment. Without the fraud we could be so much further in something that might actually work!
I believe the blood brain barrier might be damaged often in these cases so avoiding risky sports could be a good idea
When your doctor’s only advice is exercise and diet and you’ve repeatedly told them you do exercise, it’s quite obvious they have no financial incentive to help you.
Take note of this, please. Exercise is good but “a lack of exercise” is unlikely to explain your problems. An autoimmune disease is far more likely.
2nd point: humans are still confusing correlation with causation.
We know acne stops when people come out of puberty. But for some reason no one decided to test for this when testing synthetic vitamin a (retinols / accutane). They invented a drug that stunts growth, not one that cures acne.
@@user-zu1ix3yq2w thankfully there's active research into anti-inflammatory medications for Alzheimer's too, so we hope that that will help. Same with how medications can help with cardiovascular risk factors. We're still a long way to really understanding a lot of things in neurology to be honest. A lack of exercise or "the wrong diet" is definitely not the reason for most medical issues , even if exercise and diet change can help people, it's a kind of treatment. Even then, exercise and diet does not help everything.
A few months ago, I did a presentation on the two drugs I assume you were referring to (Leqembi and Aduhelm). I was pretty disappointed in a meta analysis's (Ebell, Mark H. et al) results about multiple anti-amyloid MABs' effectiveness. There were statistically significant results but not much in the way of what most would consider clinically significant.
Yes, calling these drugs breakthroughs is huge stretch. At best they give people an extra few months before needing memory care
"fancy scanner" and "image duplicatioin" instanly makes me recall the xerox scanner compresion scandal, where the scanner wanted so bad to compres that it changed data. The famous examoples were changing 6-8-9 around, 3 to 5, etc. on invoices. Are we sure that did not happen here?
Oh yeah, absolutely. This was also my first thought hearing about multiple other allegedly falsified studies with suspicious data - because that data oftentimes was in images, which looked like they may have been scanned.
Nice comprehensive, yet brief, video on the subject without resorting to "baby language" and losing the science. A great job at balancing all of these conflicting interests! A truly wonderful example of Science Education that's informative without being either impenetrable or meaningless. Thank you!
'brief', nah, it meets youtube's time-quota
One of my favorite pieces of research relates to the correlation, seemingly causitive, between HSV/shingles and AD. When you said "culprits or cooccurrences" - that is a MASSIVE difference here. The viral origin hypothesis has some of the best data I've seen as a scientist behind it, although it is limited in total quantity for obvious reasons. The cool part about that is that it provides a treatment as well - we discovered the cause by accidently treating the disease with antivirals (as in the Japanese studies), or with a vaccine (as in the welsh shingles role out).
Even if amyloid plaques cause the onset of symptoms, it still doesn't make for a cure until we figure out why the plaques are forming in the first place. I mean, it’s a start, but it’s just chasing symptoms at that point.
It is inflamation causing dysfunction like many many other neurological and psychiatric issues. Diet,blood sugar control and antiinflamatory suplementations are way effective at treating them because of it. Brain seriously cant take chronic inflamation. Some neurons are especially susceptible like dopamine.
@@exosproudmamabear558 That wasn’t my point. Treatment of symptoms is not a cure. It's like a headache; you can take medication for it but that doesn't solve the reason you have a headache and headaches are a response to a vast number of issues, some of which can lead to death.
@@jmi967 I know and thats why I told you the main reason but intermediate parts are missing of course which will be used in real treatment after all inflamation has different pathways and they need to find which pathway they neednto specifically target. But instead they are trying to get rid of plaques. Typical medical stuff tho most of the times doctors focus on increasing quality of patients life by managing symptoms instead of just curing it and that leads to worse quality of life.
I think the main reason they act like this is because most doctors do not know enough neurophysiology and even the ones research properly are limited since we dont know enough as humanity. Immun system and brain is a mystery when both those things involve everyone starts to blank amd focus on symptoms.
or maybe amyloid plaques is a response to Alzheimer's
Don't dismiss curing symptoms when the symptoms are the actual problem that needs to be solved. If someone technically has Alzheimers but their cognition is unimpaired… that's not merely a start! So the question is, "how much of the effect does clearing this away actually prevent?"
A hairbrush is among the least embarrassing things you could've left in the background.
airquotes
Hair brushing while viewing samples is one of the simple pleasures of life.
You don't know what she does with that hair brush...
Alzheimers solved!
i got an afro pick on my desk rn bro u mad?
Extremely well done video, Brovo, can';t wait to see where this channel goes
It's not even an interesting hypothesis, since it does not explain what causes the plaques to form in the first place. Equivalent to the hypothesis "tumors cause cancer".
Hey, a video on mouse models would be neat. I think there's a ton of confusion out there about how informative they can be about how humans work.
I wondered the same: will the retraction stop the race down the amyloid beta rabbit hole? Nope.
It’s pretty heartbreaking. How many barely effective drugs targeting protein buildup will it take before the field truly pivots? It should be abundantly clear by now that Alzheimer’s mice are bad models for the disease in humans, likely because they are just mimicking the protein buildup symptom, not the unknown cause.
More concerned that someone has created a way to induce alzheimers...
Hope there is progress. Watching and caring for my mom going through this is torture. The drugs they gave her made her wake up screaming every night and feel nauseous every morning. They switched them up but it had no effect whatsoever.
I am currently an aging researcher, and was, prior to this, an Alzheimer's researcher. One of my earliest mentors was an old-school physiologist from UI Urbana-Champagne (this was thirty years ago). He told me that he and his colleagues used to play a game: they would publish papers and, between them, see who could include the oldest *relevant* reference in the reference section. It's a habit I'd taken on and one that has the added effect of requiring you to follow the successive chain of references down to their source. Think of the game "telephone" where one participant whispers a message in the ear of the participant next to him, until the original message has been misunderstood and taken out of context enough times as to have no bearing whatsoever on the original. In truth, we have no idea what causes Alzheimer's disease. The best analogy I can make for the amyloid and tau hypotheses is an undergrad college party. The morning after, the house is in disarray and everything is out of place. Empty beer bottles and cigarette butts are strewn about everywhere. Naturally, the correct conclusion is to blame the party on the empty beer bottles. Or the cigarette butts. Perhaps the beer bottles "caused" the cigarette butts! Perhaps if we selectively remove the beer bottles and cigarette butts, the house will be restored to its condition prior to the party. Abandoning the analogy, what is clear is that *something* has gone wrong in the brain, and it culminates in a condition called Alzheimer's disease which has some histopathological correlates to plaques of amyloid and tangles of tau. Yet drugging either will have no effect because the appearance of both represents a near end-point in a series of (by now, irreversible) events culminating in the pathology we are familiar with. The field is hopelessly addicted to these two hypotheses and generations of career researchers have lain the tracks on which this train rides to nowhere.
I love how my lab has an identical set up for our blots. Literally the same order of invitrogen/biorad/licor reagents and devices
It might just be my old age, but I'm getting the distinct feeling that my body is out to get me.
The State Board was meeting in front of the pharmacy school when a professor's name came up for reprimand. The crowd made some noise when the name came up for falsifying data. They changed jobs. But it was seen as obvious when the published data was too clean and not reproducible. There are.conflicts of interest in many medical journals and the damage it does is huge when nobody carches it. Sometimes the same effect can happen by selectively publishing only certain resorts or other.biased studies. So many problems get through. Watch out when they change anything.
The Western Blot reminds me of how spectrographs using a prism work, by sorting based on certain characteristics by passing them through a medium.
We've known this a long time about Alzheimer's. Also removing these proteins will not solve the issue. the problem is WHY the body is putting proteins there, it doesn't do things without a reason. It likely has everything to do with crappy diets and environmental pathogens causing chronic inflammation, the waste from the healing process builds up everywhere causing issues. This is sort of like saying you can cure infections by treating the fever, no you dont.
@@DrJuanTaco exactly. It's not like mAb against amyloid even work in systemic amyloidosis!
Has diet not been controlled for with Alzheimer's research?
The treatments remind me of how we handle atherosclerosis. Lower the LDL to stop plaques from clogging arteries without locating and treating arterial hardening in the first place which risks a host of other issues.
Very nice presentation well-articulated.
Informative and funny! This was definitely a good video!
very interesting! love your in detail videos of topics i would never have known
You forgot to mention the other originally noted observation. Lipid droplets in Glia. APOE4 is worse at transporting these lipids.
I watched your video "How a Chemist Makes the Softest Bread You'll Ever Eat. You are the best.
Alzheimer's may be caused by bread. That's how little we know about triggers. There may be many.
A sober explanation, although often flying above my head I got the gist of it. In my world it reminds me of water injection to enhance ICE performance. Just because it works is no reason to pour a litre of water into your cars fuel tank then fake a dynamometer record. Anyone else doing it would at worst destroy their engine at best have it running rough. None of which takes away the undisputable fact that water injection works.
When I hear about Alzheimer’s and dementia I always think about childhood dementias like sanfilipo. Children with dementia 💔 Such heartbreaking diseases.
Has lab equipment reached the point where digital signatures are added to images?
You mean exif data?
Exif can be changed, I guess he's asking about an encrypted kind of fingerprint into the images like the Content Credentials that encrypts metadata.
Claire's doppelgänger is on Good Mythical Morning show (probably has her own sub-channel from GMM)
The evidence for retraction was that the little blobs looked too similar? Are they going based on the original sampli, on the original data, or on the published data? There's like so many computer reasons that picture could be messed up, and even more human error reasons. I mean they don't even like to retract with admission of fraud so i'd be interested in how well they actually traced down the issue with the data, wouldn't the original samples be floating around or do they degrade or get destroyed?
How fraud might guide the direction of research (in terms of what gets published and what gets funded) is sadly not that surprising given publication bias. Scientific journals can be too conservative and can take a while before accepting new measurements. A semi-recent example is the so-called “proton radius puzzle.”
Rather than treating the amaloid after it occurs why not try to find what's causing it and treat that? Probably because we don't know the cause... Let's find out. If we can prevent the amaloid build up then we will either solve the problem or learn they are not the problem (nor is their immediate cause.)
Thanks and keep up the good work!
The enlightened position is to see this as evidence of time travel.
what is your professional opinion on Ornish et al (2024) ? Does it represent a pathway to reversal of disease?
Whatever the outcome a study is not a waste of time until it becomes fraudulent.
If experiments give a negative, say unexpected, result, then you have learned something.
It is not a failure unless you screw up the process.
The video was put up by Shawn Baker, the care home owner is Hal Cranmer, I believe the title is "This is Scary"
Reasonable summary but concluding that Amyloid beta is still a good potential explanation is a very iffy place to leave things. Every anti-amyloid treatment since bapinezumab a decade ago has failed to cure the disease or even to make a difference in the progression.
Your buddy Claire has it right when she mentions trying to come up with a more complete mouse model because the mouse models have also lead down dead ends when they aren't similar enough to the cascade of causes and effects in the human pathology.
"very fancy scanner" also known as camera in a dark box
Great video!
wait till you understand that the pharmaceutical industry don't want to find cheap and effective cures but profitable remediation that are taken chronically.
Well done Clair, it was nice to hear someone pronounce “beta” correctly 🧐
I don't understand how you can know so much about AD but not mention Dale Bredesen.
Probably because Dale Bredesen is a total fraud.
Has anyone been arrested or lost their job because of this fraud?
Totally random: Is there anyway that the similar mechanisms that occur due to Prion Exposure..?? Maybe there are different types of misfolded proteins that maybe.. could cause a slow chain effect that triggers the Plaque or Taou build up over a long period of time??
Listerine for plaque removal.😂
As for the caption at 5:04. pretty sure she said 'Tau-opathy' rather than 'telepathy'.
whoops! Thanks, good catch. The mouse models aren't doing telepathy yet.
@@ACSReactions🤨.
@@ACSReactions yet (wink)
Comparatively speaking western blot aren’t that expensive I mean a single Eliza kit can be anywhere anywhere between 500 and $1500
Gotta ask, is Alzheimer’s more prevalent in the United States? If so then it must be associated with the diet.
Even if americans are more prone to alzhemiers, Correlation does not equal Causation that is a basic rule in statistics
It can be a stepping point to figuring out why americans (if they are more prone) are to alzheimers compared to other countries. But just because something is correlated to another does not mean that it is the cause. It can't even be called evidence to that conclusion either because of how many different factors other than diets people face in different regions and climates alongside population density and way more variables
Plaque from cholesterol probably
I'd ask if it can be induced in politicians who oppose universal healthcare, but seems nature is way ahead of me.
Alzheimer's is Diabetes type 3.
I don't understand why these "alleged" frauds remain "alleged" for so long. Shouldn't we have some clear prove by now? Either by reproducing the study or whoever done the study can redo these tests maybe with an independent observer.
Also isn't it odd that some other markers look like duplicates as well?
"Allegedly" simply means "claimed" or "believed".
That's different from "proven to have been done intentionally".
The paper was clearly bad and should never have been published, but that's a bit different from "I can prove in court that he made a bad paper intentionally", and without that second part, you're likely to get sued for it
@@OhhCrapGuy so it's about wether it was negligence? mhmm u i see
I think instances like this highlight the importance of 'AI scientist' in their ability to simply work without trying to meet deadlines or appeal to donors. Surely they'd still be corrupted by their humans but it would take a significant workload off the shoulders of scientists under tremendous pressure to produce results. Where they could simply had the AI tell the shareholder no with significant amounts of data that lead to what the scientist may feel. Cus u know it they felt this science in their bones that is why they lied.
What about Rapamycin?
Maybe a diabetes medication that crosses the blood brain barrier could help, diabetes can cause a limb to die because of poor blood flow and infection, and a connection between the two seems to be forming from what I've heard. I've heard somewhere that those amyloid beta clots could be the brains self defense mechanism or (own theory), it could be equitable to scarring. Hope this could be useful.
True. Some researchers believe the microglia have a key role in Alzheimer. And that the plaques cause some immune reaction that worsens the progression.
There are also similar mechanisms found with other plaques in the brain
Yo that’s crazy
Gamma frequency?
what is „m s paint“?
How are amyloid beta and tau proteins hypothesized to cause or contribute to Alzheimer's? I have a superficial understanding of the topic but would like to learn more.
They’re both considered to be symptoms of the disease rather than a cause. The video is misleading
Heavy metal build up over time.
Is nobody going to talk about that microscope?!?! is that what I think it is??? I don't even want to get into how expensive that equipment it is but as the technology gets better it'll get cheaper. I am really excited where my cross copy is going😊
There is exiting research going on however this approach is still medicalizing the treatment of symptoms. Not addressing the causes which is why slowing the progression a bit is all a drug will ever do. It is also wrong to say there are no better alternatives. Professor Robert Lustig has patients cured of Alzheimer's disease, and free of symptoms for over 8 years now when caught early enough. This is by remediating each known cause of inflammation. Mostly it's food, and environment. Everything we normally do wrong. Drug research is helpful in highlighting that only lifestyle well help.
Is it fraud or mistake?
I don't know, I forget.🤔
We need to spend more to find out if it was a waste...
Lol I feel that not wanting to run a western unless you really have to😂
I keep reading that a famuos Viennese Psychoanalyst of the XIX century helped with an Alzheimer Breakthrough...
Beta amyloid and tau were first discovered in the brains of individuals who had dementia (post mortem) more than 100 years ago, as this video states
Is that a UK accent that has been almost reduced to a non-regional American diction?
Are crispr technologies incorporated to alter the formation of these proteins that cause Alzheimer's disease
No one is using crispr in the brain because it is considered too dangerous. Crispr still has its flaws of cutting in other places and adding more mutations than wanted.
It would be interesting to see if someone did this in mice or cell culture though
did it lead us to seeing your hairbrush? Yes
I had a large volume of data collection of 10 years worth hacked from my computer for past 20 years.. im doing work on qiantum consciousness and AI and alzheimers cptsd.
Oh no, now everyone knows you brush your hair!
It's a secret!!!
Scandal! Riot!!
Her coffee mug has a pronoun. There's a comedian in England whose pronouns are "He, he, and he".
Lol, good one. Surprised this didn’t have any likes when I came across it! A shame.
I dont know enough about helium to get this joke
Eli Lilly projects on everything they can.
Uhh , could they have done this intentionally 😂.
What? Stand on the data of their predecessors without bothering to replicate or trace it back while having AI peer review their work?
Could someone have modified their test results intentionally?
@@lithunoisan meaning , anticipating that there would be more research .
@@m.c.4674 Please elaborate on your position, I don’t understand what you are trying to say.
TLDW: No and nothing changed
Thank me later
Fuck yeah, love fraud
dopamine ?
We do know what causes it. All vasular dementias are a spectrum of overactivation of the integrated stress response.
APOE4 isn't a causal factor. It just speeds it up by supplying more cholesterol to the brain, which is linked to higher IQ in those possessing that variant.
Which also causes junk to accumulate if cellular waste management, repair, and nutrient sensing arent working appropriately.
May want to look at a gene called MOF, which regulates epigenetic quality control in the brain. Nutrient sensing.
Plus, EIF2A and EIF2B, which regulate protein production quality control.
Hmm
60 Minutes recently posted a video covering a new potential Alzheimer's treatment using ultrasound. ruclips.net/video/3EfX25igUbc/видео.html
It would be awesome if there's actually a potential non-invasive non-drug treatment for this disease, which causes so much suffering to patients and families.
Hey, if your lab will do the "uncomfortable, invasive" test for free, I'll volunteer right now! ( I have that mild genetic tendency, so why not?)
PS: Western blot? Been there, done that, borreliosiis. Hey, have you noticed increased tendency of dementia with Lyme disease? Probably....Cheers...
she's mine, I need her.
Doesn't this sound like mad cow disease. Not the same but similar.?
The similarity to BSE is mentioned in Dale Bredesen's book 'the end of alzheimer's'.
There was a clip I watched few months ago, a researcher used red light therapy to treat the brain diseases,
a person with Parkinson used this method for 40 days with significant improvement. There are products in the market.
Maybe it's type III diabetes as some suggest. Care home residents in Mesa AZ were put on a strict carnivore diet, many of them had dememtia. Their children were warned, no donuts, no cookies, no candy, no carbs. Several of the residents regained their cognition, some went home to live a normal life.
Where was the study published?
Sounds fake 🤥
Did the researchers know that the blot was bad data? if so then there was no fraud. It would only be fraud if they knowingly published bad information. They could actually sue you for defamation for your use of the word.
Not going to mention statins?
I thought Nature peer reviews all its articles first. How could this even have happened?!
Because academic publishing fell the whims of capitalist logic years ago.
Nature only has to "peer review"(have other scientists actually review stuff for free) a certain percentage of their articles. Just enough for them to keep the prestigious title.
Unfortunately, peer review is not as extensive as you might think it is. Peer review is often done by unpaid volunteers with limited time
Nature definitely peer reviews its articles, but the image analysis required to spot this is probably not in the wheelhouse of peer reviewers (they'd be Alzheimer's experts, after all) and peer review is meant to look for errors and oversights, not outright fraud. This case certainly shows some vulnerability in the system, but the fact that it eventually got caught is also probably a good sign.
Reviewers are not supposed to be fraud investigators, but to evaluate if the paper is scientifically sound. The reviewer expects that the author is being honest in their reporting, and no reviewer has time to do a pixel by pixel analysis of a western blot.
@@tykos6 True and nowadays pixel analysis of western blots is something that could be easily automated with computer software (if it isn't already)
lmao first read it as Freud
The 'Evidence' for protein buildup being the 'cause' is a very poor way of stating the actual mush that is the science here.
you say "we don't 100% know" -- the correct phrase there is probably "we probably don't even 50% know".
"we're still a little bit in the dark here" 😂 no, you're "mostly in the dark here". this is a pernicious and common problem in science communication. you cannot recognize or accurately quantify how little is known. you repeatedly misrepresent the state of knowledge in casual speech. and specialists constantly do this in technical works. the tendency is to say "just a little bit is left to understand!" when this is false.
"it's not like our current best bet therapies are homeruns either" -- again, NO. they are barely BASE HITS. they are barely 25% of the way to the goal. 😂 madness. hubris. exaggeration.
What about that lady who could smell parkinsons?
what about her?
She can't smell Alzheimer's.
I don't think Alzheimer's is genetic I think it comes down to what people are eating and putting into there body.
Not really sure what this is doing on Reactions tbh...