Sylvain E. Lesné (born 1974) is a French neuroscientist and former associate professor at the Department of Neuroscience at the University of Minnesota (UMN) Medical School, known for his research in Alzheimer's disease. He is the primary author of a controversial 2006 Nature paper, "A specific amyloid-β protein assembly in the brain impairs memory". Lesné's work in the 2006 publication and others has been investigated since June 2022 on charges that he manipulated images to inflate the role of Aβ*56 in Alzheimer's. Retracted in 2024, the paper was foundational in the hypothesis that one specific toxic oligomer of the amyloid beta protein, known as Aβ*56, caused memory impairment in Alzheimer's, aligned with the prevailing amyloid hypothesis. Karen Ashe, the senior author of the 2006 Nature paper – and all authors except Lesné – agreed to retract the paper which, according to Retraction Watch, makes it the second most highly cited paper ever retracted. Responses from other researchers indicated that, while the allegations were significant, the overall impact on amyloid research was small and most Alzheimer's research was not compromised. Other researchers disagreed, and expressed concerns that the doctored images raised doubts about the amyloid hypothesis. Lesné resigned from his tenured position at UMN effective March 1, 2025.
Personal life and education 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). Jill Caroline, a Minnesota psychologist and special educator, and Lesné were married in Beauvoir-sur-Mer, France on August 14, 2010.
Early career 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.
University of Minnesota After graduating from university, Lesné was hired in 2002 as a post-doctoral research associate by Karen Ashe at the University of Minnesota. The Minneapolis Star Tribune described Ashe 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 claimed to have developed a means of measuring amyloid beta (Aβ) oligomer proteins separately inside and outside of cells. Dennis J. Selkoe, another Alzheimer's researcher, has questioned this method, saying that "it made no biochemical sense". Since 2009, Lesné had a laboratory at the UMN funded by National Institutes of Health (NIH). 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. 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. As of 2024, he was a scholar at the UMN's Institute for Translational Neuroscience. Lesné resigned from his tenured position at UMN effective March 1, 2025, after a UMN investigation flagged "data integrity" concerns in other articles he authored.
Alzheimer's research Lesné is the lead author, with Ashe and others as co-authors, of a controversial 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 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. For the paper, 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."
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