Review challenges key University of Minnesota work on Alzheimer’s disease

Allegations of duplicated or manipulated images have cast suspicion on University of Minnesota findings that have been fundamental to Alzheimer’s disease research.

An investigation published Thursday by Science questioned the findings of U, mainly researcher Sylvain Lesné, on the role of a protein in the inhibition of memory and the contribution to dementia linked to Alzheimer’s disease.

Images from a key study showed the growth of a protein, known as Aβ*56 (or alpha-beta star 56), as the mice aged and showed symptoms of dementia. The inquest called the images “apparently doctored”, raising questions about the link between the protein and the symptoms.

The report was based on concerns from Dr. Matthew Schrag, who reviewed the footage outside of his role at Vanderbilt Memory and Alzheimer’s Center in Tennessee. He reported the concerns to the National Institutes of Health, which funded much of the U.

“What I saw was a pervasive pattern in many articles,” Schrag said Thursday. “Many of these articles turned out to be high-profile, high-impact works that had a lot to do with how many people framed the problem of Alzheimer’s disease.”

The scrutiny prompted the scientific journal Nature last week to investigate a key 2006 paper by Lesné and U’s colleagues, and to encourage readers “to exercise caution when using the results” in the interval.

A spokesperson for U Medical School declined to comment Thursday other than to say the institution was aware of the claims and was following its standard process for reviewing them. An email to Lesné was not immediately returned on Thursday.

The claims hit one of the medical school’s signature research achievements over the past quarter-century – defining the role of beta-amyloid proteins in the dementia process and giving scientists a much-needed target for treating the disease. of Alzheimer’s.

Much of the work has focused on mouse maze research by Karen Ashe, an eminent professor considered by many to be shortlisted for a Nobel Prize for her work. She was co-author of many contested articles.

Schrag said he has gone public with his concerns to expedite the review and sort out what is correct so patients can confidently participate in future clinical trials for Alzheimer’s treatments. His concerns surfaced late last year on PubPeer, a website where scientists raise concerns about their colleagues’ work, including images of Western blot lab tests that identify protein levels in the blood. or fabrics.

Schrag enlarged, colorized, and inverted these images of Lesné’s studies in a way that revealed concerns about their authenticity.

Ashe addressed some of the concerns on PubPeer. In one instance, Schrag identified splice marks indicating transfer results were cut and pasted onto an image. Ashe said the marks did not exist in the manuscript submitted to Nature.

“I conclude that the linear splice marks were introduced during the processing of the manuscript,” she replied. “Most importantly, I hope you agree that my analysis indicates that the ‘splice marks’ are artifacts and that the published data is valid.”

The Science article built on Schrag’s concerns by reviewing the images with other leading dementia researchers. Experts included Dr. Dennis Selkoe of Harvard University, who shares many of the U researchers’ hypotheses about the origins of Alzheimer’s disease and cited the 2006 Nature paper in his work.

Selkoe told Science that he doesn’t agree with allegations of manipulation of certain images, but there “are definitely at least 12 or 15 images that I would agree that there is no another explanation”.

The concerns wouldn’t defeat the whole theory of amyloid proteins having neurotoxic effects that lead to Alzheimer’s disease-related dementia, but Selkoe told Science they undermine the existence of the Aβ*56 protein which is at the heart of Lesné’s research.

Regarding Ashe, he told Science, “I don’t see how she wouldn’t scrutinize anything that would later involve Aβ*56.”

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