A French researcher accused of having falsified his work on Alzheimer’s

This is information that must have caused a wave of panic to blow in some laboratories. Charles Piller, a journalist specializing in scientific investigation, dropped a small bomb in the columns of the very prestigious journal Nature; he explains that he discovered evidence of manipulation in the work of the French researcher Sylvain Lesneauthor of a research paper on Alzheimer’s disease in 2006.

the paper in question is what one might call a bestselling publication » ; in the small world of advanced neurobiology, it has established itself as a reference article since it has been cited in the documentation of more than 2200 other academic papers.

If he has been so cited, it is because he was the very first to identify Aβ* 56. This protein is very widely suspected of playing an important role in the development of Alzheimer’s disease. Indeed, it is a somewhat special class of protein; we talk about beta-amyloid, and we know that these objects tend to accumulate in the brain of patients affected by this disease.

Aβ* 56 and its equivalents are therefore at the heart of a fairly promising therapeutic avenue; many specialists now believe that getting rid of these peptides, often referred to by the term oligomers in this work, would make it possible to fight against the development of Alzheimer’s from the first signs.

The Western Blot of Discord

The whole thing therefore seemed quite solid… until whistleblower Matthew Schrag, a neurobiologist at Vanderbilt University, came to poke his nose into this strange affair. He dutifully combed through Lesné’s work, and what he found did not please him at all; he was the first to cast doubt on the results published by his counterpart.

This situation immediately caused a reaction from Science, the leading scientific magazine in which this work was initially published. Its editorial board immediately dispatched two additional experts to review this work. And they came to the same conclusions as Schrag.

They shared his interpretation claiming that images of Western Blot Would’ve been falsified. It is an extremely common and unavoidable technique in countless laboratories. It makes it possible to detect and identify proteins (Aβ* 56 in this case) using antibodies specially directed against the target.

And it turns out that neither Schrag nor the experts have succeeded in replicating the results of this Western Blot, nor has the rest of the scientific community. And that’s anything but a detail. Indeed, reproducibility is even one of the most important foundations of the whole scientific method. For a conclusion to be considered valid, it is imperative that other researchers can achieve exactly the same results at the end of a strictly identical protocol.

If this is not the case, it necessarily means that there is a problem somewhere. But this is not necessarily fraud; a difference may well come from an important factor that the researchers forgot to take into account, or from a simple measurement error, for example.

But the fact that no one manages to reproduce the results of the French researcher put the flea in the ear of the trio. At the end of their investigation, in addition to the original 2006 paper, they ended up identifying a total of “ 20 suspicious papers », all signed by Lesné.

However, they refuse to explicitly accuse him of fraud or anything else. But they also explain that it will be imperative dissect the images in question to determine whether or not they have been tampered with.

What impact on research?

This is a particularly thorny situation, because as mentioned above, this work directly served as the basis for a lot of other scientific publications which were themselves cited in other publications, and so on. Lesné’s paper is therefore at the root of a vast genealogical tree of studies which are inspired by each other.

If they have indeed been falsified, it means that the authors of all these papers have potentially lost some of their time. The Nobel-winning neurologist Thomas Südhof, interviewed by Science, is also very severe. For him, it is a waste of effort and subsidies which represent a dead loss of time for doctors and patients.

“I am speechless over these allegations“, also explains Christian Hass, head of the German Center for the Study of Neurodegenerative Diseases. “This damages the reputation of oligomer research, while researchers are doing very good work”, he laments.

Fortunately, this does not necessarily mean that it will be necessary to question all the conclusions of more than 2200 publications. Many other researchers prefer to remember the fact that this work has already made it possible to advance research against Alzheimer’s. For them, even if there is indeed a filiation, the majority of these conclusions do not depend directly on the results of Lesné.

“We should not question the work of thousands of researchers; their efforts bring us closer every day to life-saving new treatments for the millions of people affected by the disease“, says Sara Imarisio, director of research at Alzheimer’s Research UK interviewed by the Business Insider.

“The refutation of Aβ* 56 would have no impact on the vast amount of evidence in favor of the role of oligomers”, adds researcher Dominic Walsh on the specialized media ALZForum. “The paper on Aβ* 56 was only one article among others which explained that these oligomers were key elements of Alzheimer’s”, also nuances Mathias Juncker, from the University of Tübingen. “I don’t think research would have evolved otherwise without Lesné’s work.”, he adds.

It will therefore be very interesting to follow the fallout from this case. At first, we can expect investigators to attempt to authenticate Discord’s notorious Western Blot, but that will be anything but obvious.

In the meantime, you can find the very interesting reactions and comments of many researchers, including some of Lesné’s co-authors, in the comments of the post on ALZForum.