Alzheimer’s theory undermined by allegations of fabricated research

Claims that part of a pivotal 2006 study on Alzheimer’s disease may have been fabricated have rocked the research community and questioned the validity of the study’s influential findings.

Science Magazine said Thursday it found evidence that images in the much-cited study, published 16 years ago in the journal Nature, may have been tampered with.

The findings have fueled skepticism about the work of Sylvain Lesné, a neuroscientist and associate professor at the University of Minnesota, and his research, which has sparked interest in a specific assembly of proteins as a promising target for treating Alzheimer’s disease. Lesné did not respond to NBC News requests for comment, nor did he comment on Science magazine.

Science said it found more than 20 Lesné “suspect” papers and identified more than 70 cases of possible image manipulation in its studies. A whistleblower, Dr. Matthew Schrag, a neuroscientist at Vanderbilt University, raised concerns about the potential manipulation of images in several articles last year.

Karl Herrup, a professor of neurobiology at the University of Pittsburgh’s Brain Institute, who was not involved in the research, said the results were “really bad for science.”

“It’s never a shame to be wrong in science,” said Herrup, who also works at the school’s Alzheimer’s Research Center. “Much of the best science has been made by people who were wrong and proved first whether they were wrong and then why they were wrong. What is utterly toxic to science is fraud.”

For decades, a leading theory claimed that amyloid beta protein forms sticky plaques in the brain, which are the main cause of Alzheimer’s.

The 2006 study in Nature identified a subtype of the protein – Aβ*56 or “amyloid beta star 56” – as the cause of memory loss in rats.

The paper caused “a lot of buzz at the time,” said Donna Wilcock, associate dean of biomedicine at the University of Kentucky.

However, Science magazine said it had found evidence that the paper’s images — and images in other studies of Aβ*56 by Lesné — had been manipulated to inflate the protein’s role in progression to Alzheimer’s, according to experts Wilcock who reviewed the images for Science.

Other researchers have expressed concern that Lesné’s findings might not be replicated, an important part of the scientific process to confirm the validity of certain findings.

“In my own work [Aβ*56] was not a species… that we had ever observed,” said Dr. Thomas Wisniewski, Professor of Neurology at New York University’s Alzheimer’s Disease Center.

Wisniewski, who was not involved in the investigation, said he looked at the images Monday and “saw evidence of what appears to be copy and paste” to create a composite image.

Wilcock said she also noticed small areas of the images that appeared to have been “selectively enhanced.”

dr Karen Ashe, a neuroscientist and professor at the University of Minnesota who co-authored the 2006 paper, said her desire was to retract the study in its entirety, citing that trust in it had been eroded — but she claimed also that it is a revocation “does not question the amyloid beta hypothesis.”

“After working 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 has misled me and the scientific community by manipulating images might,” she said in an email statement.

Kat Dodge, a spokeswoman for the University of Minnesota Medical School, said the institution is aware of questions about the studies published by Lesné and Ashe.

“The university will follow its processes to review the issues that have raised any allegations,” she said Monday in a statement provided to NBC News.

nature exhibited a publisher’s Note on July 14, saying it was investigating the concerns about the 2006 paper and that “a further editorial response will follow as soon as possible”.

More than $1 billion in federal funding has been allocated through the National Institutes of Health for amyloid-related Alzheimer’s research. While the research suggests studies on Aβ*56 should be re-examined, experts said the theory as a whole should not be discredited.

“Further work needs to be done by other groups to specifically try to reproduce this work in other experimental models,” Wisniewski said.

Herrup said it wasn’t just Lesné’s work that influenced the direction of Alzheimer’s research over the past two decades.

“There were so many other forces that drove this conceptualization of the disease,” he said.

But such incidents can be extremely damaging to scientists and the broader research community, experts said.

“It really hurts and undermines public confidence in the scientific process,” Wilcock said. “That’s the most disturbing and exciting thing for me as a scientist.”

https://www.nbcnews.com/science/science-news/alzheimers-theory-undermined-accusations-fabricated-research-rcna39843 Alzheimer’s theory undermined by allegations of fabricated research

Fry Electronics Team

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