That 2006 paper was primarily authored by neuroscience professor Sylvain Lesné and given more weight by the name of well-respected neuroscientist Karen Ashe, both from the robust neuroscience research team at the University of Minnesota. It was Ashe who produced the transgenic mice used in the study, which genuinely do appear to have Alzheimer’s-like symptoms and that have since been used as the favored animal models for a generation of treatments. On her website, Ashe called Aβ*56 “the first substance ever identified in brain tissue in Alzheimer’s research that has been shown to cause memory impairment.”
The results of the study seemed to demonstrate the amyloids-to-Alzheimer’s pipeline with a clarity that even the most casual reader could understand, and it became one of—if not the most—influential papers in all of Alzheimer’s research. Not only has it been cited hundreds of times in other work, roughly 100 out of the 130 Alzheimer’s drugs now working their way through trials are directly designed to attack the kind of amyloids featured in this paper. Both Ashe and Lesné became neuroscience rock stars, the leaders of a wave based on their 2006 paper.
What intrigued Schrag when he came back to this seminal work were the images. Images in the paper that were supposed to show the relationship between memory issues and the presence of Aβ*56 appeared to have been altered. Some of them appeared to have been pieced together from multiple images. Schrag shied away from actually accusing this foundational paper of being a “fraud,” but he definitely raised “red flags.” He raised those concerns, discreetly at first, in a letter sent directly to the National Institutes of Health (NIH). Only when that letter failed to generate a response did Schrag bring his suspicions to others.
Now Science has concluded its own six-month review, during which it consulted with image experts. What they found seems to confirm Schrag’s suspicions.
They concurred with his overall conclusions, which cast doubt on hundreds of images, including more than 70 in Lesné’s papers. Some look like “shockingly blatant” examples of image tampering, says Donna Wilcock, an Alzheimer’s expert at the University of Kentucky.
After reviewing the images, molecular biologist Elisabeth Bik said of the paper, “The obtained experimental results might not have been the desired results, and that data might have been changed to … better fit a hypothesis.”
Should this fraud turn out to be as extensive as it appears at first glance, the implications go well beyond just misdirecting tens of billions in funding and millions of hours of research over the last two decades. Since that 2006 publication, the presence or absence of this specific amyloid has often been treated as diagnostic of Alzheimer’s. Meaning that patients who did die from Alzheimer's may have been misdiagnosed as having something else. Those whose dementia came from other causes may have falsely been dragged under the Alzheimer’s umbrella. And every possible kind of study, whether it's as exotic as light therapy or long-running as nuns doing crossword puzzles, may have ultimately had results that were measured against a false yardstick.