Review of key work questions by the University of Minnesota on Alzheimer’s disease

The allegations of duplicate or manipulated images have cast doubt on the University of Minnesota’s findings that were central to Alzheimer’s research.

An investigation published by Science Thursday questioned U’s findings, primarily by researcher Sylvain Lesne, about the protein’s role in dampening memory and contributing to dementia associated with Alzheimer’s disease.

Images in a major study showed a growth in a protein, known as Aβ*56 (or star alpha-beta 56), around the same time the mice were old and experiencing symptoms of dementia. The investigation described the images as “apparently fake”, raising questions about the link between the protein and symptoms.

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

“What I saw was a widespread pattern with too many articles,” Schrag said Thursday. “It turns out that a lot of these articles were high-profile, high-impact work and had a lot to do with the number of people who formulated the Alzheimer’s problem.”

That scrutiny prompted the scientific journal Nature last week to investigate a major 2006 paper written by Lesny and colleagues, and to encourage readers to “be careful when using the results” in the meantime.

A spokesperson for the U.S. College of Medicine declined to comment Thursday other than to say the institution was aware of the allegations and was following its standard procedures for reviewing them. An email to Lesné was not immediately returned on Thursday.

The claim hits one of the medical school’s defining research accomplishments of the past quarter century — determining the role of amyloid-beta proteins in the dementia process and giving scientists a much-needed target for Alzheimer’s disease.

Much of the work has focused on research on the mouse maze by Karen Ash, an eminent professor considered by many to be shortlisted for a Nobel Prize for her work. She has co-authored several disputed papers.

Schrag said he has voiced his concerns to speed up the review and determine what is accurate so patients can confidently enter future clinical trials of Alzheimer’s treatments. His concerns surfaced late last year on PubPeer, a website where scientists raised concerns about their colleagues’ work — including images of Western blot lab tests that determine protein levels in blood or tissue.

Schrag magnified, colorized, and mirrored those images from Lesny’s studies in ways that revealed concerns about their authenticity.

Ash responded to some concerns on PubPeer. In one case, Schrag identified paste marks indicating that the results of the smudge were cut and pasted onto an image. Asch said the signs were not present in the manuscript Submitted to Nature.

She replied, “I conclude that the calligraphic pasting marks were introduced during the processing of the manuscript.” “Most importantly, I hope you will agree that my analysis indicates that the ‘paste tags’ are artifacts and that the published data is valid.”

The Science article built on Sharrag’s concerns by reviewing the images with other prominent researchers in the field of dementia. Among the experts was Harvard’s Dr. Dennis Silko, who shares many of the U researchers’ hypotheses about the origins of Alzheimer’s disease and cited a 2006 Nature paper for his work.

Selkoe told Science he disagreed with the allegations of manipulation of some of the images, but “there are certainly at least 12 or 15 images where I agree there is no other explanation.”

These concerns won’t thwart the entire theory of amyloid proteins that have neuroprotective effects that lead to Alzheimer’s-related dementia, but Silko told Science magazine that they undermine the presence of the Aβ*56 protein that is central to Lisney’s research.

Regarding Ashe, he told Science, “I don’t see how she wouldn’t overexpress anything that is later associated with Aβ*56.”

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