Last week, some shocking allegations made concerning a prevailing theory of Alzheimer’s shook the research community, calling into question the validity of the study’s authoritative results. Apparently, part of a pivotal 2006 study of Alzheimer’s disease may have been fabricated. 

Science magazine proclaimed that it uncovered evidence that images may have been altered in the widely-cited study, published 16 years ago in the journal Nature. As a result, neuroscientist Sylvain Lesné’s work is at the epicenter of attention, suspicion, and skepticism. His findings fueled interest in a specific assembly of proteins as a promising target for the treatment of Alzheimer’s disease. Science magazine said it found more than 20 “suspect” papers by Lesné and identified more than 70 instances of possible image tampering in his studies. 

Dr. Matthew Schrag, whistleblower, and neuroscientist at Vanderbilt University, raised concerns last year about the possible manipulation of images in multiple papers.

Karl Herrup, a professor of neurobiology at the University of Pittsburgh Brain Institute who wasn’t involved in the investigation, said the findings are “really bad for science.” 

He also remarked, “It’s never shameful to be wrong in science. A lot of the best science was done by people being wrong and proving first if they were wrong and then why they were wrong. What is completely toxic to science is to be fraudulent.”

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. For decades, the leading theory stated that the amyloid beta protein formed sticky plaques in the brain that were the main cause of Alzheimer’s. 

According to Donna Wilcock, the assistant dean of biomedicine at the University of Kentucky, the paper caused “a big splash at the time.”

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

Other researchers expressed concern that Lesné’s results couldn’t be replicated, a crucial part of the scientific process to confirm the validity of specific findings.

Dr. Thomas Wisniewski, a professor of neurology at the New York University Alzheimer’s Disease Center, said, “In my own work, [Aβ*56] was not a species … that we had ever observed.” However, he looked at the images Monday and saw “evidence of what looks like copy and paste” to make a composite picture. 

Wisniewski wasn’t involved in the investigation.

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 she wishes to retract the study in its entirety. She said that confidence in it has been undermined, but she also maintained that a retraction “does not call the amyloid-beta hypothesis into question.”

She said in an emailed statement, 

“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 co-worker may have misled me and the scientific community through the doctoring of images.” 

Nature issued a publisher’s note on the study on July 14, stating that it was investigating the concerns about the 2006 paper and that “a further editorial response will follow as soon as possible.”

Through the National Institutes of Health, more than $1 billion of government funding has been directed to amyloid-related Alzheimer’s research. While the investigation suggests that studies of Aβ*56 should be opened up to new scrutiny, experts said the entire theory shouldn’t be entirely discredited.

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

And 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 driving that conceptualization of the disease,” he explained.

“It really hurts and erodes the public trust in the scientific process,” Wilcock said. “That’s what is the most disturbing and upsetting to me as a scientist.”

This will obviously have enormous implications. We will surely revisit this time and again. There’s no telling where this will go. 

https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease?

https://www.nature.com/articles/nature04533

https://www.alzforum.org/news/community-news/sylvain-lesne-who-found-av56-accused-image-manipulation

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