Two Decades of Alzheimer’s Research May Be Based on Deliberate Fraud That Cost Millions of Lives

Suspicion that something was just a little off with the model that receives almost all the funding for Alzheimer’s research ($1.6 billion last year alone) started with a fight around the drug Simufilam. The drug was pushed into trials by its manufacturer, Cassava Sciences, but a group of scientists who reviewed the drugmaker’s claims about Simufilam felt it overstated the potential. So they did what any reasonable person would do: they bought short-sell positions in Cassava Sciences stock, filed a letter with the FDA calling for a review before allowing the drug to go on trial, and hired an investigator to lend support to this position. .

As Science reports, it’s this investigator, Vanderbilt University neuroscientist and junior professor Matthew Schrag, who knocked over the whole basket of apples to find out that it wasn’t just that Cassava’s medicine was ineffective. There is good evidence that over the past 16 years almost everyone has had the wrong idea about the cause of Alzheimer’s disease. Due to fraud.

In 2006, Nature published a paper titled “A specific assembly of amyloid-β protein in the brain impairs memory”. Using a series of studies in mice, the paper concluded that “memory deficits in middle-aged mice” have been directed caused by accumulations of a soluble substance called “Aß*56. It was a particular form of a group known as “toxic oligomers” long suspected of being the possible precursors of amyloid plaques. The document then linked this condition directly to “cognitive deficits associated with Alzheimer’s disease” independent of other conditions affecting the aging brain.

The study did not come out of nowhere; it only seemed to confirm one of the many hypotheses about Alzheimer’s disease that had been circulating for many years at that time. After all, the brains of patients with Alzheimer’s disease contain plaques that can sometimes seriously alter the structure of the brain. These plaques contain amyloids. It is no exaggeration to suggest that these amyloids are the primary cause of memory loss and associated dementia. Amyloids cause plaques, plaques cause damage, damage causes Alzheimer’s disease. CQFD.

This 2006 article was primarily written by neuroscience professor Sylvain Lesné and given more weight by the name of a well-respected neuroscientist. Karen Ashe, both from the strong neuroscience research team at the University of Minnesota. It was Ashe who produced the transgenic mice used in the study, which genuinely appear to exhibit Alzheimer’s-like symptoms and have since been used as the favored animal models for a generation of treatments. On his website, Ashe called Aβ*56 “the first substance ever identified in brain tissue in Alzheimer’s disease research that has been shown to cause memory impairment.”

The results of the study seemed to demonstrate the link between amyloid and Alzheimer’s disease with a clarity that even the most casual reader could understand, and it became one of, if not the most influential paper of all. research on Alzheimer’s disease. Not only has it been cited hundreds of times in other work, but about 100 of the 130 Alzheimer’s drugs currently in trial are directly designed to attack the type of amyloid presented in this article. Both Ashe and Lesné have become neuroscience rock stars, leaders of a wave based on their 2006 paper.

What intrigued Schrag when he returned to this seminal work were the images. Images in the article that were supposed to show the relationship between memory problems and the presence of Aβ*56 appeared to have been altered. Some of them appeared to have been pieced together from multiple images. Slantwise hesitated to accuse this seminal document of being a “fraud”, but he definitely raised “red flags”. He raised those concerns, quietly at first, in a letter sent directly to the National Institutes of Health (NIH). It was only when this letter failed to generate a response that Schrag shared his suspicions with others.

Now Science concluded its own six-month review, during which it consulted with image experts. What they found seems to confirm Schrag’s suspicions.

They agreed with his general conclusions, which cast doubt on hundreds of images, including more than 70 in Lesné’s papers. Some look like “surprisingly egregious” examples of image tampering, says Donna Wilcock, an Alzheimer’s disease specialist at the University of Kentucky.

After reviewing the images, molecular biologist Elisabeth Bik said of the article: “The experimental results obtained might not have been the desired results, and these data could have been edited to… better match a hypothesis”.

If this fraud were to turn out to be as large as it first appears, the implications go far beyond the simple misuse of tens of billions in funding and millions of hours of research over the past two decades. . Since that 2006 publication, the presence or absence of this specific amyloid has often been treated as diagnostic of Alzheimer’s. This means that patients who died of Alzheimer’s disease may have been misdiagnosed as having something else. Those whose dementia stemmed from other causes may have been falsely dragged under the umbrella of Alzheimer’s disease. And every possible type of study, whether as exotic as light therapy or long as nuns doing crossword puzzles, may have ultimately had results that were measured against a false measure.

In the face of the potential fraud unearthed by Schrag, it’s not like the world has changed overnight.

Four months after Schrag submitted his concerns to the NIH, the NIH turned around and awarded Lesné a five-year grant to study… Alzheimer’s disease. This grant was awarded by Austin Yang, program director at the NIH’s National Institute on Aging. Yang also happens to be another of the co-authors of the 2006 article.

Science has carefully detailed the work done in the analysis of the images. Other researchers, including a 2008 paper from Harvard, have noted that Aβ*56 is unstable and there appears to be no evidence of this substance in human tissue, making its targeting literally worse than useless. However, Lesné claims to have a method to measure Aβ*56 and other oligomers in brain cells which served as the basis for a series of additional papers, all of which are now in doubt.

There seems to be no doubt that oligomers may play a role in cognitive impairment. However, this role may not be as direct or as prominent as the 2006 article and subsequent articles in Lesné suggested. It is quite possible that the specific Aβ*56 oligomer can’t even exist apart from Ashe’s transgenic mice.

And it seems very likely that in the last 16 years most of the research on Alzheimer’s disease and most of the new drugs going into trials have been based on a paper that, at best, has changed the results of his findings to make them appear more conclusive, and at worst is outright fraud.

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