The Alzheimer’s fiasco: Scientific Fraud in NIH

Alzheimer’s is the most terrible, mind-shattering disease of our time. We citizens given the task to the prestigious National Institutes of Health to slay the dragon. Staffed by the crème de la crème, leading scientists from all over the world, there could be no questioning of its scientific expertise and its capacity to take on this role. Agency leadership was entrusted to Dr. Eliezer Masliah, the scientific leader for the neuroscience division in the NIH.

In the past few weeks much of his research has been deeply questioned exposed as perpetrating a massive fraud. See Picture Imperfect in Science, Charles Piller. He was fired last week, an unprecedented move for such an institution.

This means that much of the giant institutional edifice underlying the Federal government’s approach to solving the problem has been invalidated.

I have been following and writing about this problem in this blog since 2018. I have particularly focused on the so-called cause of Alzheimer’s in the guise of amyloid plaques. Since the inception of my interest in 2018 I have insisted that this focus is just plain wrong.

Little did I realize that some of this was due to the fraud by Masliah and, even more shockingly, by another prominent researchers overseas, including in France.

In this pos I am going to summarize my growing concern about what now seems to have been a huge and cleverly organized conspiracy. It took many of the world’s stop scientists and scientific leaders with it. But not just them alone. If has fooled top executives in some of the world’s top health companies and pharmaceuticals.

 It even swept up top nonprofits who became fellow-travelers and promoters of the scientific theses and did their own thing to promote it to other scientists in an ever-widening scheme to bring in others, including ultimately thousands of victims of patients and their afflicted relatives.

Even though I nailed the problem, I didn’t suspect that it could all be due to fraud and lack of curiosity and exploration. That is, until it got too big to hide. And until finally even the research establishment itself couldn’t ignore it any longer.

We Urgently Need a Manhattan Project for Alzheimer's!

January 13, 2018,  Yep, The Founding Date of My Muckraking efforts

It all started with what I announced as Really Bad News. To wit: Pfizer had just terminated its work in developing a drug to cure Alzheimer’s. And even more grim news: Axovant had just announced that its Alzheimer’s drug just failed its trials too. It turns out that there had been  been a long series of failures in this area (“The List of Failed Alzheimer’s Drug Treatments Keeps Growing”). I wondered why.

For all this bad news was covered up by drug companies who saw huge profits and clinicians and hospitals who saw this as the ultimate gravy train. Nobody was going to stop this train in its tracks.

Unfortunately I had predicted this myself some time ago (“Maybe Alzheimer’s isn’t a Brain Disease?”). I pointed out that the amyloid plaque theory was just not working out and looked to be false. I cited other research which pointed to completely different causes and asked why that approach wasn’t being supported.

But Alzheimer’s is forever. And once someone gets it, it ties down others who have to give them care, often 24/7. And let’s just state the bald truth. We haven’t made any progress whatsoever with it, unlike cancer. Little did I realize that a big reason for this failure was systematic, and due to scientific fraud at the highest levels of government.

We still don’t even know how the brain really works. The Federal Government has launched the so-called BRAIN initiative to promote basic research into how the brain works. But tell me this: what is more important right now, finding out how the brain really works or solving the Alzheimer’s problem? My money is on fixing the dyke before we’ve all drowned. Draining the fens can come later.

Alzheimer’s represents a massive systemic failure in healthcare, as well as socially. Once big companies start pulling out what else is there to do? Do we have to wait for more failures and more surrenders before we finally get the message? It’s time for real, hard-core action.

I wrote this in 2018…. Jan 13, 2018

My conclusion: We’ve got to get the NIH out of the process or see how they can be watered down. They are totally the wrong people to lead a breakthrough project such as the one I envisage. Otherwise, they’re going to play favorites again and we’ll never find a solution.

OMG did I actually write that! Then! And look now!!

The Alzheimer’s situation is a rapidly mounting crisis.

So, I started to think about the scientific issues in the problem.

But that took me a couple of years to figure out. None of us are getting any younger.

Alzheimer’s: What if they aren’t tangles but knots?

I’ve been really concerned about the lack of progress on Alzheimer’s. So in early 2018 I posted on the topic (“We urgently need a Manhattan Project for Alzheimer's!” 13 January, 2018).

In my post I pointed out the research into the disease wasn’t working out because it was concerned only with amyloid plaque, that none of the drugs developed for amyloid had worked, and that the NIH was partly at fault because it insisted that research must be directed to amyloid, and if it wasn’t, it didn’t fund the proposal and that was why no other promising approaches were being followed.

At the time I talked with a number of researchers who insisted that the amyloid approach would work out, and that I was a layman so didn’t know what I was talking about. Let us scientists handle it, moron! We know what we’re doing!

Well, another day another dollar. Not 5 months later the NIH changed its tune and announced a strategy to go after new and promising approaches (“NIH summit delivers recommendations to accelerate therapy development for Alzheimer’s disease May 2018”). Could my post have had some tiny impact after all?

There’s been a suspicion for some years, also not fully explored because of the NIH’s de facto moratorium on new research approaches, that Alzheimer’s is actually a prion disease, in fact a double-prion disease. Yes, both amyloid and tau are forms of prions.

Ok so I’m a layman and I don’t know diddly about it. But crazy is my business. Here’s where I’m going with this.

One of the newest areas of mathematics has been the mathematical theory of knots. Topology generally has been around for donkeys’ years but it’s only recently that the math wizards have been decoding how knots work. And of the latest areas it’s the stability of a knot. Turns out you can predict this using some fancy math footwork including the number of crossings involved and the direction in which the rope segments twist as the knot is pulled tight.

OK so you might say, interesting, but how the hell would you untie those knots anyway, even if this idea holds any water at all?

Well, what’s CRISPR for? What about all the recent more sophisticated variants? Isn’t cutting and pasting DNA actually untying, tying retying knots anyway? Aren’t we finding new ways of doing this stuff with every passing day? Give it a shot, before we both get Alzheimer’s, dummy!

Thinking Outside the Universe?

Well, why not? Doesn’t it sound like it’s a lead of sorts? And don’t we need leads? And isn’t it the case that often the true breakthroughs come from other disciplines which seem to have no connection whatsoever to the problem you’re trying to solve?

It seems to me that the Alzheimer’s field still isn’t thinking enough outside the box. Yes, the NIH and the fields fixation with amyloid has been broken, but that doesn’t mean the scientists in this area have become freethinkers yet. I think we are going to need a lot more free-thinking before we break the back of this terrible disease.

Little did I know that Eliezer Masliah was a big part of the problem, but since he was the key to the NIH efforts that was never going to be called out.

But what the Feds did all along was play along with the like of Eliezer Masliah. We fired a culprit so now were just lost 10 years, or more. And we don’t even know diddly about his fellow travelers, and the out and out charlatans. How’s that for the bankruptcy of government!

Forget Any Hope of a Cure for Alzheimer’s in The Foreseeable Future

Jan 25, 2022

See, two more years have elapsed while I continue mull to this over. Surely the scientist, the government and the august presence of the NIH could never be pushing down the wrong road, one that was just a huge illusion, a conspiracy of silence, or even worse

Yeah, there’s tons of research but the Alzheimer’s community, well-meaning as it is, is wedded to bureaucratic approaches which have totally stymied any true innovation.

Definition of Insanity Applies

OK, everyone will say how much research is going on in the field and the setbacks are just temporary, yada. But the failures in the Alzheimer’s community look to be systemic and a result of mental rigidity. So, things look like they are getting even worse, not better.

Did you see that yet another Alzheimer’s drug hit the dirt last week? The trial has been going on for several years. Big setback for Roche, the company behind it. It’s a recurring pattern for the Alzheimer’s field. Are the companies, researchers, lobbyists, philanthropists doing something wrong? Let’s take a closer look at that thesis.

First just to acknowledge the obvious. The Alzheimer’s field has just registered a blockbuster failure with Aduhelm from Biogen. The drug just didn’t work at addressing the core problem with Alzheimer’s, the loss of cognitive performance. That’s been the story with all the drugs that have failed.

It’s looking increasingly likely that the amyloid/tau hypothesis, which sees these plaques as being the cause of Alzheimer’s, is wrong and that there is a deeper cause that hasn’t been unraveled yet. Yet there are still more amyloid/tau drugs, that many are counting on to break the logjam, to hit the airwaves soon. The odds are that they are going to fail too.

You know the one about the definition of insanity? Doing the same thing again and again and expecting a different result. That’s where the Alzheimer’s research community is right now with no signs of recognizing they have dug themselves into a deep hole. I am talking about government, universities, company R&D organizations and nonprofits.

The Alzheimer’s Guardians Are Ineffective

Even the Alzheimer’s nonprofits, the community committed to supporting research into Alzheimer’s, has fallen into that hole. They supported Aduhelm, even when it was obvious it didn’t work. Now they are generally taking the same stance with the amyloid drugs soon to be released. It looks like even the proponents of a research-based solution have drunk Kool-Aid. When the nonprofits for Alzheimer’s fall for the idee fixe which is just plain wrong, what hope is there for anyone else to solve the problem?

OK I know. The people in the Alzheimer’s world are well-meaning, driven by the tragedy which has befallen them and their loved ones. They are not deliberately putting sawdust in the wheels. Actually, they are doing all they believe they can. But nonetheless they have been weighed down by a culture of not rocking the research boats. Now I believe that the continuing failures of the research have led them all to essentially give up.

So, I hear my readers say to me, can you do any better? What solutions do you have to offer?

Yep, I do. Read on.

We have to acknowledge a few truths.

1.            Alzheimer’s will not be cured in our lifetimes.

2.            Most so-called causes will just lead down rabbit holes.

3.            “Alzheimer’s” is actually numerous diseases each with different causes, some radically different.

4.            The initial breakthroughs are going to be repurposed drugs that work for a small part of the problem, e.g., Viagra, and other drugs that seem to have a palliative effect.

5.            These incremental breakthroughs will not come from professional researchers with PhDs in neuroscience since they usually have perverse incentives, to get grants that keep them employed for many years to find a, yes, you guessed it, cure that is always distant. But it puts food on their tables and often puts them on a tenure track, even if the drug fails.

6.            Professional neuroscience types are too heavily invested in their field to be able to think outside the box; it will be innovators who aren’t invested in current theories who will find the answers.

7.            We will find the answers not by looking for the right “science” but for the right behaviors – out of the box types, often viewed as bonkers in the field – who try totally new things.

8.            Until the Alzheimer’s community focuses on getting innovators rather than scientists, they’re not going to find the answers.

There’s a trend amongst some companies to involve younger people in STEM research to train them for possible future research in the field. That’s a noble but largely useless approach. Here’s what I would do:

·         Identify under-20s who have a passion for finding a solution because they already have family members who are afflicted.

·         These under-20s should be assessed to ensure that they are true innovators who can think outside the box. That almost guarantees you don’t want these youngsters to have degrees in science or especially PhDs.

·         Pay them big grants to give them an incentive to drop out of school to focus on the problem and bring in others like them.

·         Give those who come up with winning drugs large cash prizes to reward them for winning.

·         Get serious about promoting true innovators, truly bonkers doers, not promote the powder-puff academic theories and tenure-seekers in vogue right now.

The Alzheimer’s community, including the nonprofits, need to get off their butts and bring in true innovators, not the bureaucrats we have now. That includes reforming the biggest big pharmas and nonprofits, not to mention government research bureaucrats, to give them a sharp edge, which they signally lack currently.

If they don’t do that you can say sayonara to ever getting a cure or anything else for Alzheimer’s. During that time losing millions of minds that we can never get back.

That’s the true tragedy we all face right now.

That’s what Masliah stood for.

The Alzheimer’s Research Fiasco – 1% Fraud, 99% Groupthink

We have posted on numerous occasions that the global research industry for Alzheimer’s was taking the wrong route. Even we didn’t suspect that there was deliberate fraud.

The Low Road

For many years we have posted our opinion that worldwide research for Alzheimer’s has taken the wrong path. That path of course was the amyloid hypothesis. We said that the hypothesis was likely wrong and that researchers were being funded by the likes of the NIH because it was fashionable (Forget Any Hope of a Cure for Alzheimer’s in the Foreseeable Future). Researchers were being funded because they were looking for a sure thing for tenure. But even we didn’t suspect that there was fraud involved.

So if you want to see the tragic details check out the Daily Kos: Two decades of Alzheimer's research may be based on deliberate fraud that has cost millions of lives.

There’s even more at Science: Potential fabrication in research images threatens key theory of Alzheimer's disease.

The fraud started in 2006 with a French scientist (Professor Sylvain Lesné) whose data was faked but the results were so convincing that he took in numerous other regular and honest scientists who based their research on his results leading to a snowball effect.

The results are that the much of the entire edifice of science around Alzheimer’s research globally is all wrong. That would be the hypothesis that amyloid and tau clumps in the brain are the cause of Alzheimer’s. And that, my friends, explains the decade of failures we have had in new drugs, all based on the theory. The latest was the drug Aduhelm from Biogen, which received fast approval from the FDA. A lot of egg, on lots of scientific faces.

I have been posting for several years about the problem that in the Alzheimer’s research community only proposals involving the amyloid route have been funded by the NIH.

Of course, I was ignored. As an outsider and non-scientist that’s something I must accept.

But it shows the risk we have in the science of groupthink and the reliance on so-called experts, above all experts in the government.

And there’s far more blame than that. How about the numerous pharmaceutical companies that went with the flow and lost billions for their shareholders? Not to mention the people who became afflicted with the disease while scientists meandered on with a lot of wishful thinking but little or no critical edge.

It's not that the Alzheimer’s scientific community and its followers are not able to be trusted. Doubtless the vast majority ae sincere, honest and committed to their research mission. But it shows that scientists are just as capable of succumbing to groupthink as we mere mortals, perhaps even more so because they erroneously believe that the culture of scientific endeavor protects them from flawed thinking and approaches.

Not that any of this is to say that the Alzheimer’s research community is atypical, and the rest of scientific research is all copasetic. Far be it from the real case.

Scientific research globally is riddled with perverse incentives from the obsessive search for tenure (and hence continued employment), pressure to publish scientific papers, no matter if they are faked, the inability to replicate most papers, the worthlessness of negative results (when the reverse should be the case) and so on such as issues like dosages and side effects.

Scientists and leaders in the Alzheimer’s field have gotten a big black eye. It’s going to be difficult to trust them after this disaster, not because they are dishonest, which they aren’t, but because they have proved themselves too gullible and too prone to group-thinking.

That’s a terrible recipe for spending vast amounts of money. They look for all the world like the Defense Department and some of the flawed thinking there too. That goes for scientists and executives in pharmaceutical companies, government scientists and bodies such as the NIH and the FDA, and yes hitherto trusted nonprofits.

Can these bodies be trusted to clean things up and choose an effective course of action? Can they be trusted to launch initiatives which are genuinely innovative, something they have rejected during this whole sorry history? That is suddenly in question, and we won’t know the answer for some time yet. The Alzheimer’s research community has got to clean up its act and convince John Q. Public that they really have done so.

Hidden Jewels

There are unheralded and good things going on in the field such as the recent emergence of Alzheimer’s biomarkers. Without drugs for clinical use, they are not much use but it’s a start.

We need to search out genuine innovators in the field. They will exist but we have to identify and support them before they get squelched by the traditionalists. Most of the innovators in Alzheimer’s have been frozen out so finding these people and getting them back in the saddle won’t be easy. Once bitten twice shy. But it’s got to be done.

But we have just lost 20 years. There’s no getting that back.

Wishful Thinking or Just Tragic Delusion in Alzheimer’s?

Yet another Alzheimer’s drug, lecanemab, is hitting the FDA seeking approval, but looks to be of marginal benefit at best. Wishful thinking is squelching the radical actions we need to take to break through to a cure. Without radical thinking we will never get a cure for Alzheimer’s.

More is Less

The history of Alzheimer’s drugs continues to be depressing. After the debacle of Aduhelm (and its precursors), there’s a new kid on the block, lecanemab from Biogen. Unfortunately, despite all the hype from its developer Biogen, it looks depressingly similar too. At best it’s marginal in clinical impact. At worst it’s dangerous with brain bleeding (resulting in at least 2 deaths so far) being a major concern, not to mention significant brain shrinkage.

Why can we be so sure that the cognitive impact of lecanemab is so problematic? How about the view of a respected medical journal for starters?

“The Lancet” the authoritative UK medical journal, has pointed out that the Biogen drug trial shows a 0.45-point difference on an 18-point scale in the cognitive score of patients taking lecanemab versus those on placebo.

That’s a marginal benefit at best, and probably not clinically meaningful, it argued. The Biogen study states that the patients experienced a 27% lower decline in cognitive performance than would otherwise have occurred without the drug. How do you even see and measure this in a way that a patient or a carer can actually see and feel?

Right now, I fear it’s the psychological environment surrounding the Alzheimer’s situation that is even more depressing than the clinical results. For Alzheimer’s patients and their carers there’s just no hope in sight. By that I mean, no cure and nothing to help even mitigate the suffering for patients and their careers.

Yet numerous nonprofits and researchers maintain the hype surrounding amyloid drugs. That approach risks promoting a dangerous delusion and prevents radical action being taken. Right now, radicals are the only sensible way to go.

The proximate cause of all this is the collective delusion is the amazingly widespread idea that amyloid is the cause of Alzheimer’s. Clearly that isn’t the case otherwise any of the numerous amyloid-targeting drugs would have worked to at least some degree.

Mercifully, after way too long defending the amyloid thesis researchers are now turning their attention to new lines of research. We’re gradually backing out of this research dead end. New and promising leads are emerging (See “New Discovery Could Explain Why We've Been Misled Over the Cause of Alzheimer's”: ScienceAlert; “What Causes Alzheimer’s? Scientists Are Rethinking the Answer. “Quanta Magazine). But that is going to take time, 5-10 years at least. In the meantime, we are facing a situation where nothing works.

There’s no point in sugar-coating the bitter pill that we’re getting absolutely nowhere with the current amyloid research efforts Otherwise we’re just setting the whole field back, to everyone’s detriment. We need to be clear-eyed, realistic, hyper-realistic even, clinical in the purest meaning of the word. We need to be negative enough to shock the politicians into taking bold action.

The more we rely on wishful thinking and the tragic delusion that things are getting better, the more we reduce the pressure on researchers and politicians to foment the research revolution that is needed to get a cure.

The worst is for our friends and relatives as they disappear down dark rabbit holes, never to be able to live fruitful and productive lives.

The Author

Charles Piller

Charles Piller writes investigative stories for Science.

He previously worked as an investigative journalist for STAT, the Los Angeles Times, and The Sacramento Bee, and has reported on public health, biological warfare, infectious disease outbreaks, and other topics from the United States, Africa, Asia, Europe, and Central America.

Charles has won numerous journalism honors, including the 2016 AAAS/Kavli Science Journalism Award, the American Society of Tropical Medicine and Hygiene Communications Award, the National Council on Crime and Delinquency PASS Award, the First Amendment Coalition Free Speech & Open Government Award, a 2023 Award for Excellence in Science Communications (from the National Academies of Sciences, Engineering, and Medicine and Schmidt Futures), and the 2023 and 2024 National Institute of Health Care Management Trade Journalism Award.

Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer’s, Charles’s book for Simon & Schuster/One Signal Publishers, will be published in February 2025. He previously authored two investigative books about science and has testified before the U.S. Senate about his investigations of government compliance with the Freedom of Information Act, and workplace electronic surveillance.