Academic journal

Key discovery may be wrong, questioned research

  • Findings from a seminal 2006 Alzheimer’s paper appear fabricated, a survey finds.
  • More than 2,200 subsequent studies have referenced the finding – and can also be invalidated.
  • Disease experts said there was still huge progress in other avenues of research.

A landmark 2006 study on Alzheimer’s disease may contain fabricated results, according to an investigation by Science magazine.

The investigation revealed evidence suggesting several instances of image manipulation in the work of Sylvain Lesné, a researcher working at the University of Minnesota and author of the 2006 study.

The paper, which is cited by more than 2,200 academic papers as a reference, sparked interest in a specific protein called Aβ*56 as a promising target for early intervention in Alzheimer’s disease.

Aβ*56 is a beta-amyloid. Beta-amyloids are proteins that have been observed to clump together in the brain, a phenomenon generally thought to be linked to the development of Alzheimer’s disease. Several different types of these proteins are potential targets for drugs to treat Alzheimer’s disease.

Whistleblower Matthew Schrag, a neuroscientist at Vanderbilt University, first reported concerns about the images to the NIH in January 2022. Science asked two experts in image analysis to review Lesné’s published work. They echoed Shrag’s concerns.

They identified a total of 20 “suspicious papers” written by Lesné, 10 of which had to do with Aβ*56, per Science.

The publication stopped short of alleging misconduct or fraud, saying the original images would need to be investigated for the manipulation to be confirmed.

The most “obvious” effect of this alleged manipulation would be “a waste of NIH funding and a waste of thinking in the field,” Nobel laureate and Stanford University neuroscientist Thomas Südhof told Science. .

Several anonymous researchers told Alzforum, an outlet focused on Alzheimer’s disease, that they tried to replicate the results but were unable to. Work like this is often not widely disseminated because it is difficult to publish results that invalidate previous work in academic journals.

“Although misconduct is rare, misconceptions inserted into key nodes in our body of scientific knowledge can distort our understanding,” Shrag told Science.

Nature, the academic journal that published the 2006 paper, is investigating allegations about the paper, according to an editor’s note.

This is the latest blow to the field of beta-amyloid research in Alzheimer’s disease, which has recently come under intense scrutiny after scientists raised concerns about the evidence base supporting the idea that the FDA-approved drug Aducanumab can improve cognition in people with Alzheimer’s disease.

While the claims about Lesné’s work are concerning, they do not undermine the field of amyloid protein research and Alzheimer’s disease, Alzheimer’s Research UK and the Alzheimer Society said in statements seen by Insider.

“Despite these claims, we must not allow the work of thousands of Alzheimer’s researchers to be undermined – their tireless efforts are bringing us closer to lifesaving new treatments for the millions of people living with the disease,” said Sara Imarisio. , head of research at Alzheimer’s. Research UK said in a statement seen by Insider.

“There are legitimate questions and criticisms of the amyloid hypothesis, but such questions are a perfectly normal and necessary part of science,” she said.

A co-author of Lesné’s papers, Karen Hsiao Ashe, supports the role of Aβ*56 in Alzheimer’s disease, stating that scientists in her lab “regularly and reproducibly detect Aβ*56” in lab mice, she wrote in a comment on Alzforum’s article.

Science has been unable to find evidence of image manipulation in Ashe’s work which is not co-authored with Lesné.

Lesné could not be reached by Science when they asked for comment.