Sylvain Lesné
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Sylvain E. Lesné (born 1974) is a French
neuroscientist A neuroscientist (or neurobiologist) is a scientist specializing in neuroscience that deals with the anatomy and function of neurons, Biological neural network, neural circuits, and glia, and their Behavior, behavioral, biological, and psycholo ...
and former associate professor at the Department of Neuroscience at the
University of Minnesota The University of Minnesota Twin Cities (historically known as University of Minnesota) is a public university, public Land-grant university, land-grant research university in the Minneapolis–Saint Paul, Twin Cities of Minneapolis and Saint ...
(UMN)
Medical School A medical school is a tertiary educational institution, professional school, or forms a part of such an institution, that teaches medicine, and awards a professional degree for physicians. Such medical degrees include the Bachelor of Medicine, ...
, known for his research into
Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
. He is the primary author of a controversial 2006 ''
Nature Nature is an inherent character or constitution, particularly of the Ecosphere (planetary), ecosphere or the universe as a whole. In this general sense nature refers to the Scientific law, laws, elements and phenomenon, phenomena of the physic ...
'' 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 In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relativ ...
of the
amyloid beta Amyloid beta (Aβ, Abeta or beta-amyloid) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor prot ...
protein, known as Aβ*56, caused
memory impairment Amnesia is a deficit in memory caused by brain damage or brain diseases,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be temporarily caused by t ...
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 Retraction Watch is a blog that reports on retractions of scientific papers and on related topics. The blog was launched in August 2010 and is produced by science writers Ivan Oransky (Former Vice President, Editorial ''Medscape'') and Adam Ma ...
, 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 Luc-sur-Mer (, literally ''Luc on Sea'') is a commune in the Calvados department in the Normandy region in northwestern France. Population Sights * The "Maison de la Baleine" created by Jean Chabriac. On 15 January 1885 a 40-ton,19-metre ...
, a small town in the
Normandy Normandy (; or ) is a geographical and cultural region in northwestern Europe, roughly coextensive with the historical Duchy of Normandy. Normandy comprises Normandy (administrative region), mainland Normandy (a part of France) and insular N ...
region In geography, regions, otherwise referred to as areas, zones, lands or territories, are portions of the Earth's surface that are broadly divided by physical characteristics (physical geography), human impact characteristics (human geography), and ...
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 The University of Caen Normandy (French: ''Université de Caen Normandie''), also known as Unicaen, is a public university in Caen, France. History The institution was founded in 1432 by John of Lancaster, 1st Duke of Bedford, the first rector ...
. 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 Beauvoir-sur-Mer (, literally ''Beauvoir on Sea'') is a commune in the Vendée department in the administrative region of the Pays de la Loire, France. Population See also *Communes of the Vendée department The following is a list of the ...
, 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 In biochemistry, immunostaining is any use of an antibody-based method to detect a specific protein in a sample. The term "immunostaining" was originally used to refer to the immunohistochemical staining of tissue sections, as first described by ...
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 (; ) is a mass media in France, French daily afternoon list of newspapers in France, newspaper. It is the main publication of Le Monde Group and reported an average print circulation, circulation of 480,000 copies per issue in 2022, including ...
'' 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 ''The Minnesota Star Tribune'', formerly the ''Minneapolis Star Tribune'', is an American daily newspaper based in Minneapolis, Minnesota. As of 2023, it is Minnesota's largest newspaper and the List of newspapers in the United States, seventh- ...
'' 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 Amyloid beta (Aβ, Abeta or beta-amyloid) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor prot ...
(Aβ)
oligomer In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relativ ...
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 The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...
(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 Associate professor is an academic title with two principal meanings: in the North American system and that of the ''Commonwealth system''. In the ''North American system'', used in the United States and many other countries, it is a position ...
in the Neuroscience Department in 2016, and given
tenure Tenure is a type of academic appointment that protects its holder from being fired or laid off except for cause, or under extraordinary circumstances such as financial exigency or program discontinuation. Academic tenure originated in the United ...
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 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 In academic publishing, the lead author or first author is the first named author of a publication such as a research article or audit. Academic authorship standards vary widely across disciplines. In many academic subjects, including the natural ...
, with Ashe and others as co-authors, of a controversial 2006 report published in ''Nature''. The paper, "A specific
amyloid-β Amyloid beta (Aβ, Abeta or beta-amyloid) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor prot ...
protein assembly in the brain impairs memory", suggested the Aβ*56
oligomer In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relativ ...
(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 A mouse (: mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
began to decline and age with
dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...
. ''
Science Science is a systematic discipline that builds and organises knowledge in the form of testable hypotheses and predictions about the universe. Modern science is typically divided into twoor threemajor branches: the natural sciences, which stu ...
'' 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 ''The Guardian'' is a British daily newspaper. It was founded in Manchester in 1821 as ''The Manchester Guardian'' and changed its name in 1959, followed by a move to London. Along with its sister paper, ''The Guardian Weekly'', ''The Guardi ...
'' 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 ''The Atlantic'' is an American magazine and multi-platform publisher based in Washington, D.C. It features articles on politics, foreign affairs, business and the economy, culture and the arts, technology, and science. It was founded in 185 ...
'' likens publication in ''Nature'' to a "career high-water mark", reflecting especially important findings. ''
The Daily Telegraph ''The Daily Telegraph'', known online and elsewhere as ''The Telegraph'', is a British daily broadsheet conservative newspaper published in London by Telegraph Media Group and distributed in the United Kingdom and internationally. It was found ...
'' states that the "seminal research paper" led to increased
drug research Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for regula ...
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 in
Sophia Antipolis Sophia Antipolis is a 2,400 hectare technology park in southeast France, and as of 2021 home to 2,500 companies, valued today at more than 5.6 billion euros and employing more than 38,000 people counting more than 80 nationalities. The park is ...
, 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."


2022 investigation

A July 2022 publication in ''Science'' authored by
Charles Piller Charles Piller is an American investigative journalist and author who writes for ''Science'' magazine . He has published books on the history of both biological warfare and Alzheimer's disease. Journalism Prior to writing at ''Science'', Pille ...
questioned the authenticity of
Western blot The western blot (sometimes called the protein immunoblot), or western blotting, is a widely used analytical technique in molecular biology and immunogenetics to detect specific proteins in a sample of tissue homogenate or extract. Besides detect ...
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 Vanderbilt University (informally Vandy or VU) is a private university, private research university in Nashville, Tennessee, United States. Founded in 1873, it was named in honor of shipping and railroad magnate Cornelius Vanderbilt, who provide ...
neuroscientist, raised concerns in a
whistleblower Whistleblowing (also whistle-blowing or whistle blowing) is the activity of a person, often an employee, revealing information about activity within a private or public organization that is deemed illegal, immoral, illicit, unsafe, unethical or ...
report that images were falsified, casting doubt on the association between the Aβ*56 protein and dementia symptoms. Schrag told ''
USA Today ''USA Today'' (often stylized in all caps) is an American daily middle-market newspaper and news broadcasting company. Founded by Al Neuharth in 1980 and launched on September 14, 1982, the newspaper operates from Gannett's corporate headq ...
'' the images had similarities to what one would expect from software like
Photoshop Adobe Photoshop is a raster graphics editor developed and published by Adobe for Windows and macOS. It was created in 1987 by Thomas and John Knoll. It is the most used tool for professional digital art, especially in raster graphics editin ...
. The editors of ''Nature'' responded with a July 14, 2022 note stating that they were aware of and investigating the concerns and that "readers are advised to use caution when using results reported therein". See lay summary
"Aβ Star is Born? Memory Loss in APP Mice Blamed on Oligomer"
Alzheimer Research Forum Alzheimer Research Forum (ARF), or Alzforum is a website which uses web technology to accelerate research into Alzheimer's disease. History The website was founded in 1996 by June Kinoshita, funded by an anonymous philanthropic foundation, and ...
, March 17, 2006.
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 The Office of Research Integrity (ORI) is a U.S. government agency that focuses on research integrity, especially in health. It was created when the Office of Scientific Integrity (OSI) in the National Institutes of Health (NIH) and the Office of ...
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 ''Science Signaling'' is a peer-reviewed scientific journal that is focused on mechanisms of cell communication. It is published online weekly by the American Association for the Advancement of Science (AAAS). The editor-in-chief is John F. Foley, ...
'', has issued two expressions of concern, and two other journals,''
The Journal of Neuroscience ''The Journal of Neuroscience'' is a weekly peer-reviewed scientific journal published by the Society for Neuroscience. It covers empirical research on all aspects of neuroscience. Its editor-in-chief is Sabine Kastner (Princeton University), who s ...
'' and ''
Brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
'', have issued corrections on articles associated with Lesné and his UMN co-workers.
Retraction Watch Retraction Watch is a blog that reports on retractions of scientific papers and on related topics. The blog was launched in August 2010 and is produced by science writers Ivan Oransky (Former Vice President, Editorial ''Medscape'') and Adam Ma ...
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. Lesné's work in the 2006 publication and others has been investigated since June 2022. 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 Harvard Medical School (HMS) is the medical school of Harvard University and is located in the Longwood Medical and Academic Area, Longwood Medical Area in Boston, Massachusetts. Founded in 1782, HMS is the third oldest medical school in the Un ...
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. , Lesné had not commented. Ashe stated via email in 2022 that "it is devastating to discover that a colleague may have misled me and the scientific community ... t is alsodistressing that a major scientific journal has blatantly misrepresented the implications of my work." ''The Daily Telegraph'' states that the "authors of the Minnesota paper have defended their original findings" and support the role of amyloid as a cause of Alzheimer's. ''USA Today'' reported that Ashe had started the process to retract the ''Nature'' paper, but that had not been done as of July 29, 2022 because six of the eight co-authors would not sign off on the request. She stated via email that "... the figures in question were manipulated in a way that made them look nicer but did not affect one word in the paper". Defending the work, she said that the image adjustments "should not have occurred", but called them "non-material" and "inconsequential" to the research overall.


2024 retraction

In May 2023, the ''Star Tribune'' reported that the senior author of the study, Karen Ashe, was using new techniques to re-do the work reported in the 2006 ''Nature'' study, this time without Lesné, and that she stated "it's my responsibility to establish the truth of what we've published". Ashe's new article was published in March 2024 in the journal iScience. In May 2024, Ashe announced that the 2006 publication would be retracted, although she stated that the manipulated images did not affect the study's conclusions; according to
Retraction Watch Retraction Watch is a blog that reports on retractions of scientific papers and on related topics. The blog was launched in August 2010 and is produced by science writers Ivan Oransky (Former Vice President, Editorial ''Medscape'') and Adam Ma ...
, this makes it the most highly cited paper ever retracted. The only co-author who did not agree with retraction was Lesné. ''Nature'' published retraction of the article on June 24, 2024, noting that the edited images showed "excessive manipulation, including splicing, duplication and the use of an eraser tool".


Impact on Alzheimer's research

Responses from some researchers in 2022 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. If studies were manipulated, Jeremy Olson stated in 2022 in the ''Star Tribune'' that "thinking on the causes of the disease and dementia" could change. Olson wrote that the allegations "wouldn't scuttle the entire theory of amyloid proteins", but "Selkoe told Science that they undercut the existence of the Aβ*56 protein that is central to Lesné's research." A
Massachusetts General Hospital Massachusetts General Hospital (Mass General or MGH) is a teaching hospital located in the West End neighborhood of Boston, Massachusetts. It is the original and largest clinical education and research facility of Harvard Medical School/Harvar ...
researcher, Rudolph E. Tanzi, said the alleged manipulation "had virtually zero effect on progress" in Alzheimer's research and characterized statements about its effect on the overall field and the amyloid hypothesis as "hyperbole". ''USA Today'' stated in 2022 that experts have "downplayed" the impact the ''Nature'' paper had on drug discovery research. Alzheimer's researchers or organizations from Australia, France, and the UK state that the general theory behind the amyloid hypothesis remains valid. Selkoe, who ''Science'' describes as "a leading advocate of the amyloid and toxic oligomer hypotheses", opined that the "broader amyloid hypothesis remains viable" and referred to the alleged image manipulation as "what really looks like a very egregious example of malfeasance that's squarely in the Aβ oligomer field". Sara Imarisio of
Alzheimer's Research UK Alzheimer's Research UK (ARUK) is a dementia research charity in the United Kingdom, founded in 1992 as the Alzheimer's Research Trust. Alzheimer’s Research UK funds scientific studies to find ways to treat, diagnose and prevent all forms of ...
said:
"These allegations are extremely serious. ... The amyloid protein is at the centre of the most influential theory of how Alzheimer's disease develops in the brain. But the research that has been called into question is focused on a very specific type of amyloid, and these allegations do not compromise the vast majority of knowledge built up during decades of research into the role of this protein in the disease."
The U.S.
National Institute on Aging The National Institute on Aging (NIA) is a division of the U.S. National Institutes of Health (NIH), located in Bethesda, Maryland. The NIA itself is headquartered in Baltimore, Maryland. The NIA leads a broad scientific effort to understand ...
issued a statement saying:
... the Aβ*56 oligomer was one of many being explored at the time ... immunotherapies targeting Aβ monomers (a single 'unit' of Aβ), other types of oligomers, and the longer amyloid fibrils have been the focus of studies ... there is still a strong scientific rationale for continuing to explore approaches that target different aspects and collections of the amyloid protein.
Following Lesné's 2025 resignation, Schrag was critical of the delay. According to Piller, Schrag stated: "Accountability aslong 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."


Legacy

Writing in 2022 in ''The Atlantic'', David Grimes commented that the Lesné matter exemplified the
publish or perish "Publish or perish" is an aphorism describing the pressure to publish academic work in order to succeed in an academic career. Such institutional pressure is generally strongest at research universities. Some researchers have identified the p ...
dilemma, in which pressure to publish in academia can lead to wasted research dollars and inaccurate findings. A
National Public Radio National Public Radio (NPR) is an American public broadcasting organization headquartered in Washington, D.C., with its NPR West headquarters in Culver City, California. It serves as a national Radio syndication, syndicator to a network of more ...
broadcast on the show ''
All Things Considered ''All Things Considered'' (''ATC'') is the flagship news program on the American network National Public Radio (NPR). It was the first news program on NPR, premiering on May 3, 1971. It is broadcast live on NPR affiliated stations in the United ...
'' linked instances of scientific misconduct to competition for funding. In a February 13, 2025 book review of
Charles Piller Charles Piller is an American investigative journalist and author who writes for ''Science'' magazine . He has published books on the history of both biological warfare and Alzheimer's disease. Journalism Prior to writing at ''Science'', Pille ...
's '' Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer's'', Carl Elliott wrote that "shocking was that some of Lesné's work had come from the lab of Karen Ashe, one of the most acclaimed neuroscientists in the field", noting that the University of Minnesota had the "dubious distinction of producing two of the five most highly cited scientific papers ever to be retracted" according to
Retraction Watch Retraction Watch is a blog that reports on retractions of scientific papers and on related topics. The blog was launched in August 2010 and is produced by science writers Ivan Oransky (Former Vice President, Editorial ''Medscape'') and Adam Ma ...
.


Notes


References


External links

Personal
Sylvain Lesné
University of Minnesota Medical School * *
The Lesné Laboratory
Independent coverage
Science podcast July 22, 2022
with Charles Piller, author of ''Science'' article
Timeline
from neurologylive.com {{DEFAULTSORT:Lesne, Sylvain Alzheimer's disease researchers French neuroscientists University of Minnesota faculty University of Caen Normandy alumni Living people 1974 births People from Calvados (department)