Alzheimer’s researcher Sylvain Lesné under suspicion of forgery

Frankfurt When Sylvain Lesné published a widely acclaimed study on a possible central cause of Alzheimer’s disease in the journal “Nature” 16 years ago, he, the main author, was just 32 years old. His work has been cited in the professional world for years as evidence for the thesis that protein deposits are responsible for the deadly disease.

Now there are increasing indications that the French neuroscientist manipulated his publication: his case has been shaking medical science for a few days.

It is not only discussed to what extent Lesné has damaged the entire Alzheimer’s research. The question is also whether his work has led to bad investments worth billions in a research approach that has not yet produced any effective drugs. At least that’s how the specialist magazine “Science” intones the matter. The magazine had exposed the whole thing.

In a 2006 research paper, Lesné, born in 1974, presented the protein called Abeta*56 as one of the causes of Alzheimer’s dementia. The study by the biochemist, who has been working at the University of Minnesota since 2002, responded to the then widespread hypothesis that protein deposits – so-called amyloid plaques – can be held responsible for the brain disorders in Alzheimer’s dementia.

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This was documented in the study with a series of recordings that showed the protein deposits in the brains of study participants. The recordings were probably fake, as the specialist magazine “Science” announced at the end of July. More than 20 publications by the Frenchman are said to have contained manipulated images, according to “Science”.

“Amyloid Mafia” is said to have disadvantaged scientists with a different approach

Neuroscientist Matthew Schrag got the ball rolling last year. He had come across inconsistencies in the illustrations of Lesné’s works. Schrag turned to “Science”, which researched for more than six months with the support of experts and is now making serious allegations against Lesné.

>> Read here: New drugs: The pharmaceutical industry uses artificial intelligence for drug research

Should these be confirmed, not only Lesné would have to answer. Supervisors, co-authors and specialist magazines that published the articles should also ask themselves why the manipulations were not noticed.

“It is devastating to realize that a former collaborator has misled me and the scientific community about editing images,” writes Karen Ashe, co-author and director of Lesné on the internet platform Alzforum. The University of Minnesota has opened an investigation into Lesné, Ashe said.

At the same time, however, the scientist defends herself against an accusation raised implicitly by “Science”: According to this, the research work on Abeta*56 encouraged a series of ultimately misinvested drug studies that target the mechanism of action of amyloids, precisely these protein deposits in the brain. According to Ashe, there have not been any clinical studies that have specifically addressed this molecule.

The journal Science had argued that Lesné’s work had helped strengthen the amyloid hypothesis in the development of new drugs. About half of all Alzheimer’s funding flows into such projects. Scientists focusing on other possible causes of Alzheimer’s, such as immune disorders or inflammation, would lament being sidelined by the “amyloid mafia.”

Alzheimer’s disease remains incurable

However, previous drugs that target plaques have not yet proven effective. Not even the drug Aduhelm from Biogen, which was approved last year. Although it had yielded conflicting efficacy results in two main studies, the US regulatory agency approved it. Biogen has meanwhile withdrawn the drug from the European market.

This shows how high the therapeutic emergency is for Alzheimer’s disease, which affects more than 30 million people worldwide. To date, there is no drug that can cure the disease.

The last approvals in this area were made around the turn of the millennium. The active ingredients introduced at the time, such as donepezil from the US group Pfizer or memantine from the Frankfurt pharmaceutical company Merz, only target the symptoms of the disease and do not attack the cause.

Various scientists, however, put the role of Lesné’s work in Alzheimer’s research into perspective. “I had never heard of the name Lesné before the scandal,” Alzheimer researcher Giovanni Frisoni from the Neurocenter at the University of Geneva told the “Neue Zürcher Zeitung”. “Lesné’s work is by no means the decisive one,” agrees his colleague Robert Perneczky from the University of Munich. Both emphasize that the studies on the Lesné molecule Abeta*56 were not the most important basis for drug developments in recent years.

Neuroscientist Mathias Jucker, professor and director at the Hertie Institute for Clinical Brain Research at the University of Tübingen, also comments on Alzforum: “The implications of the ‘Science’ article are exaggerated.” The Lesné/Ashe paper has much less influence on the direction in the research field than is claimed in “Science”. “I don’t think that the research field would have developed differently without the Lesné work,” says Jucker.

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