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Sylvain Lesné

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Sylvain E. Lesné is a 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.[1] He is the primary author of a 2006 Nature paper[2] that is foundational in the hypothesis that a toxic oligomer of the amyloid beta protein, known as Aβ*56, is a cause of memory impairment in Alzheimer's, as part of the prevailing amyloid hypothesis.[1] As of July 2022, his work is being investigated on charges that he manipulated images to inflate the role of Aβ*56 in Alzheimer's.[3]

Personal life and education

Lesné was raised in Luc-sur-Mer, a small town in the Normandy region in northwestern France.[4] His parents are Bertrand and Marie Carmen Lesné.[5] He holds a master's degree in biochemistry and has a PhD with a major in neuroscience from the University of Caen Normandy.[6] 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).[7] He married Jill Caroline, a Minnesota psychologist and special educator, in Beauvoir-sur-Mer, France on August 14, 2010.[5]

University of Minnesota

After graduating from university, Lesné was hired in 2002[6] by Karen Ashe at the University of Minnesota.[1]

Since 2009,[8] Lesné has had a laboratory at the UMN funded by National Institutes of Health (NIH).[1][9] Between 2008 and 2012, Lesné has received $774,000 in NIH grants to study Aβ*56, in addition to over $7 million for Alzheimer's research, according to the Minneapolis Star Tribune.[8]

Lesné is also a researcher at the UMN's N. Bud Grossman Center.[10]

Alzheimer's research

Lesné is the lead author, with Ashe and others as co-authors, on an influential 2006 report published in Nature[11] that suggested the amyloid beta*56 protein oligomer (known as amyloid beta star 56, or Aβ*56[8]) as a cause of Alzheimer's disease.[1][12] The 2006 study proposed that Aβ*56 was responsible for the memory deficits that occur in Alzheimer's.[11] According to the Star Tribune, images from the study showed the Aβ*56 protein growing as mice began to decline and age with dementia.[3]

As of early 2022, Science says it was the fifth-highest cited paper in Alzheimer's research, with approximately 2,300 other articles citing it;[1] 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.[11] The Daily Telegraph states that the "seminal research paper" led to increased drug research funding worldwide.[13]

2022 investigation

A July 2022 publication in Science authored by Charles Piller questioned the authenticity of images used in Lesné's research;[1] Piller alleges, based on a six-month investigation,[13] that images may have been doctored to emphasize the role of Aβ*56 in Alzheimer's.[8] Matthew Schrag, a Vanderbilt University neuroscientist,[1] raised concerns in a whistleblower report that images were falsified,[13] casting doubt on the association between the Aβ*56 protein and dementia symptoms.[3]

Lesné is the leading researcher overseeing or instigating the work in about 10 disputed studies.[8][11] He is being investigated by the UMN as of July 23, 2022.[11]

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".[2][8] The NIH, where Schrag lodged the whistleblower report, are also investigating the matter, and could decide to pass it on the United States Office of Research Integrity if the complaints are found valid.[13]

Alzheimer's researcher John Forsayeth commented that Ashe had been guilty of a "major ethical lapse" in oversight of the data and Dennis Selkoe said he did not understand how Ashe failed to "hyperscrutinize" the data considering reactions to the 2006 Nature report. Piller writes that Lesné's work was already being queried before his investigation, and other researchers were unable to replicate the results.[1] As of July 22, 2022, Lesné had not commented; Ashe had declined to comment on the investigation conducted by the UMN, but she stated via email that: "Having worked for decades to understand the cause of Alzheimer’s disease, so that better treatments can be found for patients, it is devastating to discover that a colleague may have misled me and the scientific community ... [it is also] distressing that a major scientific journal has blatantly misrepresented the implications of my work."[8][a] 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.[13]

If studies were manipulated, the Star Tribune reports that "thinking on the causes of the disease and dementia" could "fundamentally shift".[8] Selkoe told Science that the "broader amyloid hypothesis remains viable" and that what "looks like a very egregious example of malfeasance [is] squarely in the Aβ oligomer field".[1] Sara Imarisio of Alzheimer's Research UK said:[13]

"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."[13]

Notes

  1. ^ See also Ashe's July 22 response posted on the Alzheimer's forum.[14]

References

  1. ^ a b c d e f g h i j Piller C (21 July 2022). "Blots on a field?". Science. 377 (6604).
  2. ^ a b Lesné S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, Gallagher M, Ashe KH (March 2006). "A specific amyloid-beta protein assembly in the brain impairs memory". Nature. 440 (7082): 352–7. doi:10.1038/nature04533. PMID 16541076. Archived from the original on July 22, 2022. Retrieved July 22, 2022.
  3. ^ a b c Olson J (July 21, 2022). "Review questions key work by University of Minnesota on Alzheimer's". Star Tribune. Archived from the original on July 24, 2022. Retrieved July 24, 2022.
  4. ^ "People: Sylvain Lesné". The Lesné Laboratory. Retrieved July 22, 2022.
  5. ^ a b "Caroline-Lesne". Forum Communications Company. September 18, 2010. Archived from the original on July 24, 2022. Retrieved July 24, 2022.
  6. ^ a b Lesné SE (2013). "Breaking the code of amyloid-β oligomers" (PDF). International conference on psychology, autism, and Alzheimer's disease. OMICS Group Conferences. Retrieved July 22, 2022.
  7. ^ "Catalog record for Lesné's thesis". WorldCat. Retrieved 24 July 2022.
  8. ^ a b c d e f g h Olson J (July 22, 2022). "University of Minnesota scientist responds to fraud allegations in Alzheimer's research". Star Tribune. Archived from the original on July 23, 2022. Retrieved July 22, 2022.
  9. ^ "The Lesné Laboratory". Sylvain Lesné. Retrieved July 22, 2022.
  10. ^ Wroge L (February 3, 2015). "With aging population, Alzheimer's a main focus". Minnesota Daily. Retrieved July 22, 2022.
  11. ^ a b c d e Glenza J (July 23, 2022). "Critical elements of leading Alzheimer's study possibly fraudulent". The Guardian. Retrieved July 23, 2022.
  12. ^ Lerner M (February 13, 2012). "Dr. Karen Ashe: Stalking Alzheimer's". Star Tribune. Archived from the original on October 17, 2016. Retrieved July 22, 2022.
  13. ^ a b c d e f g Knapton S (July 21, 2022). "'Manipulated' Alzheimer's data may have misled research for 16 years". The Daily Telegraph. Archived from the original on July 22, 2022. Retrieved July 23, 2022.
  14. ^ "Sylvain Lesné, Who Found Aβ*56, Accused of Image Manipulation". alzforum.org. July 22, 2022. Retrieved July 23, 2022.

Personal

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