Sylvain Lesné

Sylvain E. Lesné (born 1974) is a French neuroscientist and associate professor at the Department of Neuroscience at the University of Minnesota (UMN) Medical School, known for his research into Alzheimer's disease.

Sylvain E. Lesné was born in 1974 and raised in Luc-sur-Mer, a small town in the Normandy region in northwestern France.

His parents are Bertrand and Marie Carmen Lesné.

Lesné holds a master's degree in biochemistry and has a PhD with a major in neuroscience from the University of Caen Normandy.

His doctoral thesis (2002) was "Régulation d'expression et du métabolisme d'APP au cours des pathologies dégénératives" (Regulation of APP expression and metabolism during degenerative pathologies).

After graduating from university, Lesné was hired in 2002 as a post-doctoral research associate by Karen Ashe at the University of Minnesota.

Ashe was described by the Minneapolis Star Tribune as a "distinguished professor considered by many to be on the short list for a Nobel Prize for her work".

Ashe in turn has described Lesné as her "brilliant postdoctoral fellow"; he had developed a means of measuring amyloid beta (Aβ) oligomer proteins which could be injected into rats.

He is the primary author of a 2006 Nature paper that is foundational in the hypothesis that one specific toxic oligomer of the amyloid beta protein, known as Aβ*56, is a cause of memory impairment in Alzheimer's, aligned with the prevailing amyloid hypothesis.

As of May 2023 Lesné's work in the 2006 publication and others is being investigated on charges that he manipulated images to inflate the role of Aβ*56 in Alzheimer's. Responses from other researchers indicate that, while the allegations are of significant concern, the overall impact on amyloid research is small and most Alzheimer's research is not compromised.

Lesné is the lead author, with Ashe and others as co-authors, on an influential 2006 report published in Nature.

The paper, "A specific amyloid-β protein assembly in the brain impairs memory", suggested the Aβ*56 oligomer (known as amyloid beta star 56 and Abeta*56 ) as a cause of Alzheimer's disease.

The 2006 study proposed that Aβ*56 was responsible for the memory deficits that occur in Alzheimer's. According to the Star Tribune, images from the study showed the Aβ*56 protein growing as mice began to decline and age with dementia.

Science says it was the fifth-highest cited paper in Alzheimer's research as of early 2022, with approximately 2,300 other articles citing it.

The Guardian says the paper was "highly influential" and calls it "one of the most cited pieces of Alzheimer's disease research in the last two decades", writing that it has "dominated the field" of research.

The Atlantic likens publication in Nature to a "career high-water mark", reflecting especially important findings.

The Daily Telegraph states that the "seminal research paper" led to increased drug research funding worldwide.

Lesné was listed as of May 13, 2022 at UMN Medical School's Wall of Scholarship recognizing faculty who "must have first or last author credits on a publication that has been cited at least 1,000 times".

Other scientists have not been able to replicate the results specific to Aβ*56 and whether it exists is questioned; several Alzheimer's researchers stated in July 2022 on the website Alzforum that they have long been skeptical of the Aβ*56 findings.

Frédéric Checler, a lab director at the Institute of Molecular and Cellular Pharmacology in Sophia Antipolis, France told Le Monde in 2022 that the 2006 Nature publication raised suspicions early on, saying: "It is extremely difficult to obtain a pure aggregate protein, and to be certain that its nature remains the same after its purification."

A July 2022 publication in Science authored by Charles Piller questioned the authenticity of Western blot images used in Lesné's research; Piller's report alleges, based on a six-month investigation, that images may have been doctored to emphasize the role of Aβ*56 in Alzheimer's. Matthew Schrag, a Vanderbilt University neuroscientist, raised concerns in a whistleblower report that images were falsified, casting doubt on the association between the Aβ*56 protein and dementia symptoms.

Schrag told USA Today the images had similarities to what one would expect from software like Photoshop.

The editors of Nature responded with a July 14, 2022 note stating they were aware of and investigating the concerns raised, that a "further editorial response [would] follow as soon as possible", and that "readers are advised to use caution when using results reported therein".

The NIH, where Schrag lodged the whistleblower report, is also investigating the matter, and could decide to pass it on the United States Office of Research Integrity if the complaints are found valid.

Lesné is the leading researcher overseeing or instigating the work in about ten disputed studies as of 2022; as of May 2023, according to the Minneapolis Star Tribune, images have been questioned on 20 articles he has authored.

Another journal, Science Signaling, has issued two expressions of concern, and two other journals,The Journal of Neuroscience and Brain, have issued corrections on articles associated with Lesné and his UMN co-workers.

Retraction Watch states that Ashe co-authored some of the disputed papers, and that the authors in the disputed work do not overlap except for two from UMN Department of Neuroscience.

On the corrected paper in Brain, Ashe and Lesné are the senior and first authors.

Piller did not find the same image inconsistencies in other work published by Ashe or Vivien without Lesné as a co-author.

UMN is investigating the reports as of May 2023.

Alzheimer's researcher John Forsayeth commented that Ashe had been guilty of a "major ethical lapse" in oversight of data and Dennis Selkoe, a Harvard Medical School neurologist, said he did not understand how Ashe failed to "hyperscrutinize" data considering reactions to the 2006 Nature report.

Piller writes that Lesné's work was already being queried before his investigation, when other researchers were unable to replicate the results.

Since 2009, Lesné has had a laboratory at the UMN funded by National Institutes of Health (NIH).

Jill Caroline, a Minnesota psychologist and special educator, and Lesné were married in Beauvoir-sur-Mer, France on August 14, 2010.

Denis Vivien, a French cell biologist and neuroscience professor who oversaw Lesné's doctoral work and published with Lesné, says Lesné produced some immunostaining images which Vivien thought suspect; others were unable to replicate Lesné's data.

Vivien withdrew a paper that was to be published with Lesné, and told Le Monde in 2022 that he had long ago ceased having any personal or scientific contact with Lesné.

He received $774,000 in NIH grants to study Aβ*56 through 2012, in addition to over $7 million for Alzheimer's research through 2022, according to the Star Tribune.

Lesné was named an Associate Professor in the Neuroscience Department in 2016, and given tenure according to the Lesné Lab website.

He was an associate director at the UMN's N. Bud Grossman Center for Memory Research and Care, where Ashe serves as director.

He is a scholar at the UMN's Institute for Translational Neuroscience as of 2022.