Scientific fraud case undermines research on the “amyloid cascade”

Paris, Friday July 29, 2022 – Several hypotheses exist to explain Alzheimer’s disease, one of the most popular is that of “amyloid cascade” : amyloid plaques are formed by the abnormal accumulation of a protein called “β-amyloid”then they “are deposited between nerve cells located in the gray matter of the cerebral cortex, causing dysfunction of the connections between neurons”summarizes the Alzheimer Foundation on its site.

“This hypothesis was put forward for the first time in 1991, it originated from the family forms of Alzheimer’s”tells the Parisian Jean-Charles Lambert, research director at Inserm.

A study published in 2006 in Nature reinforced this hypothesis. Its main author is a Frenchman, Sylvain Lesné, trained in Caen and at the time a researcher at the University of Minnesota. It relates in particular to the amyloid beta protein 56 (Aβ*56). Injected into mice, it caused memory problems in them. What to do with Aβ*56 “a star suspect” in Alzheimer’s disease, reports at the time Nature.

“Sylvain Lesné’s contribution was to find the form in which peptides are the most toxic and to show that cognitive functions are altered with the accumulation of plaques, which is easily measured in rodents. While in soluble form, β-amyloids are less troublesome. It is especially accumulated in oligomers that they have effects on the patient “explains Professor Philippe Amouyel, Director General of the Alzheimer Foundation at Sciences et Avenir.

Dozens of falsified figures and images

However, according to an investigation by the magazine Science, carried out following an alert from a Canadian neurologist, Dr. scientific literature and brought the amyloid cascade theory to the fore.

The investigation carried out by the Science teams indicates that dozens of figures published in the article base published in 2006, and images of protein detection plates, would have been falsified, which casts doubt on the validity of the results published. .

To date, the researchers involved deny any misconduct, but several experts interviewed by the journal Science confirm their impression that this data has been manipulated.

Dr. Schrag, who had not publicly revealed his role as a whistleblower prior to this article in Science, avoids the word of ” fraud “ and does not claim to have proven fault. This would require access to original, complete and unpublished images and, in some cases, to raw digital data.
“I focus on what we can see in the published images, and describe them as red flags, not definitive conclusions”he told Science.

The authors “seem to have composed figures by assembling parts of photos from different experiences”declares as for her, always to Science, Elisabeth Bik.

“The experimental results obtained may not have been the desired results, and these data may have been modified to … better fit a hypothesis.” »

Let us add further that the results of the 2006 study published in Nature have never been replicated…

It should also be noted that the marketing in the United States of two drugs based on the role of the Aβ*56 protein: simufilam and the monoclonal antibody aducanumab had largely aroused controversy as the results of clinical studies were mixed and/or or disputed.

Consequences to be tempered

With these revelations, the world of research around Alzheimer’s disease is in suspense, while the role of
“amyloid cascade” has taken an important place in recent years.

“The majority of people clearly separate the fraudulent side, intolerable and we can never do enough to denounce it, and the fact that these results do not call into question the amyloid cascade hypothesis. We are above all in a battle of specialists ”tempers Luc Buee, director of the research center “Lille Neuroscience & Cognition”with the Parisian.

“Aβ*56 is one of the possible forms of oligomers in this hypothesis, but it is far from being the only one. One fraudulent job will not invalidate thousands of other jobs”
also highlights Jean-Charles Lambert.

Finally, note that Nature has added a “editor’s note” in the 2006 study for “urge readers to exercise caution” with its results, the time to study these suspicions of fraud.


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