Sylvain Lesné, a neuroscientist accused of image manipulation in a seminal Alzheimer’s disease paper in Nature, resigned last week from his tenured professorship at the University of Minnesota Twin Cities (UMN). The move follows a 2.5-year investigation in which the university found problems with several other papers on which Lesné is an author. The Nature study has already been pulled, but the school has asked that four more of Lesné’s papers be retracted.
The resignation, effective 1 March, was first reported by the Minnesota Reformer. Lesné did not respond to a request for comment. UMN spokesperson Jake Ricker said, “The university has identified data integrity concerns impacting several publications and has been in touch with those journals to recommend retraction of the publications, where appropriate.”
As a postdoc, Lesné worked in the lab of neuroscientist Karen Ashe. In 2006, they published a study in Nature that seemed to show a cause-effect relationship between a protein—amyloid-beta *56—and memory loss in rats. Those symptoms seemed to resemble the memory problems that afflict Alzheimer’s patients.
The paper buoyed confidence in the so-called amyloid hypothesis of Alzheimer’s, which holds that a brain buildup of amyloid proteins provokes a cascade of biochemical damage to neurons and other cells, leading to dementia. At the time the idea faced increasing skepticism after failures of experimental drugs designed to arrest or slow cognitive decline by reducing amyloid. Proponents of the hypothesis celebrated the finding, and the paper became one of the most cited Alzheimer’s papers of this century.
In 2022, Science first reported the story of Lesné’s potential misconduct, which extended beyond the Nature paper to nearly 20 others, several co-authored by Ashe. She was not implicated in the apparent image doctoring, although she was the principal investigator for the Nature study and gained fame and increased research funding in the years that followed. The paper’s key Western blots—images that display the presence and concentration of proteins—showed signs of having been altered digitally in ways to improperly support the experimental hypothesis that soluble amyloid-beta *56 was toxic to brain cells.
The paper was retracted in 2024, at the request of nearly all the authors—including Ashe. (Lesné alone disagreed.) Ashe and her co-authors conceded that images appeared to have been doctored, although she continues to defend the validity of the findings.
During an interview in January 2024, when this reporter was researching a book on Alzheimer’s, Ashe said that after Science exposed the problems, Lesné “vehemently denied” having doctored the images. But during a tense conversation with Ashe and UMN research integrity officials, “he wasn’t able to enlighten us on how it happened,” Ashe said. “I had no idea that he would ever do something like this, because he seemed fine—very bright, very hardworking.” She added: “I do really regret that Sylvain did what he did in my lab.”
Vanderbilt University neuroscientist Matthew Schrag, working independently from his university duties, discovered most of the suspect papers by Lesné and colleagues. Among those, Ricker says UMN flagged four—three of which concerned amyloid-beta *56, including one co-authored by Ashe—for possible retraction. Together, those four papers have been cited about 600 times in scientific journals (Neurobiology of Aging in 2011, The Journal of Neuroscience in July and November 2012, and Science Signaling in 2017).
Schrag believes the university took too long to act. “Accountability in this case is long overdue. The University of Minnesota’s inconsistent, incomplete, and delayed actions have seriously harmed their reputation and done a disservice to the field of Alzheimer’s research,” he says. “At a time when public confidence in our national scientific enterprise is especially vulnerable, the lack of leadership on such a clear-cut and important case is lamentable.”
