A seminal 2006 study of Alzheimer's disease might contain fabricated results, an investigation from Science magazine found. The investigation uncovered evidence suggesting several instances of image manipulation in the work of Sylvain Lesné, a researcher working at the University of Minnesota and an author of the 2006 study. The paper, which is cited by more than 2,200 academic papers as a reference, launched 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 in the brain, a phenomenon that is widely believed to be linked to the development of Alzheimer's disease. Several different types of these proteins are potential targets for drugs treating Alzheimer's. Whistleblower Matthew Schrag, a neuroscientist at Vanderbilt University, first flagged his concerns about the images to the NIH on January 2022. Science asked two image analysis experts to review Lesné's published work. They echoed Shrag's concerns. They identified a total of 20 "suspect papers" authored by Lesné, 10 of which had to do with Aβ*56, per Science. The publication stopped short of alleging misconduct or fraud, stating that the original images would have to be investigated for manipulation to be confirmed. The most "obvious" effect of this alleged manipulation would be "wasted NIH funding and wasted thinking in the field," Nobel laureate and Stanford University neuroscientist Thomas Südhof told Science. Several unnamed researchers told the Alzforum, an Alzheimer's-focused outlet, that they tried to reproduce the results but could not. Work like this is often not reported widely, as it is difficult to publish results that invalidate previous work in academic journals. "Even if misconduct is rare, false ideas inserted into key nodes in our body of scientific knowledge can warp our understanding," Shrag told Science. Nature, the academic journal that published the 2006 paper, is investigating the allegations about the paper, according to a publisher's note. This is the latest blow to the field of beta-amyloid research in Alzheimer's, which has come under scrutiny recently after scientists raised concerns about the evidence base supporting the idea that FDA-approved drug Aducanumab can improve cognition in people with Alzheimer's. Though the allegations into Lesné's work are concerning, they do not compromise the field of research into amyloid proteins and Alzheimer's disease, Alzheimer's Research UK and the Alzheimer's Society said in statements seen by Insider. "Despite these allegations, we should not allow the work of thousands of Alzheimer's researchers to be undermined – their painstaking efforts are bringing us closer to vital new treatments for the millions of people living with the disease," 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, stands by the role of Aβ*56 in Alzheimer's, stating that staff scientists in her lab "regularly and reproducibly detect Aβ*56" in lab mice, she wrote in a comment on Alzforum's article. Source
