For nearly two decades, Alzheimer’s disease research, research funding, and prescribed drugs have been centered around a 2006 research paper hypothesizing that the cognitive decline causing the debilitating disease is due to buildup in the brain of a protein called the amyloid beta (Aβ) protein. But a recent investigation is questioning whether the data in the study was fabricated—threatening one of the most cited and influential Alzheimer’s studies of all time.1
Millions of Dollars Funneled Into Alzheimer’s Research
The amyloid beta protein research was conducted by neuroscientist Sulvain Lesné, PhD, MSci, of the University of Minnesota, Twin Cities. His 2006 paper proposed that the Aβ protein caused dementia in rats. In years following, Dr. Lesné won academic prizes and received a five-year National Institutes of Health (NIH) grant to continue his research. His research has been cited nearly 2,300 times and the NIH may have provided as much as $280 million in research funding based upon his theory. His work was also aggressively promoted by the Alzheimer’s Association and several drugs trials were executed based upon his research.1
A six-month investigation by award winning reporter Charles Piller published in Science broke the news of the claimed fabrications.2 Piller’s work was aided by Matthew Schrag who has long criticized the approval of the Alzheimer’s drug Aduhelm (aducanumab) by the U.S. Food and Drug Administration (FDA). Aduhelm was approved despite 10 of 11 FDA panel members voting against its approval due to Aβ drugs failing to show any benefit.3 Schrag’s own research also contradicted the research behind another Aβ protein-targeting drug known as Simufilam.
In August 2021, Schrag was hired by attorneys to investigate patient benefit claims behind Simufilam. The attorney’s clients, two prominent neuroscientists, believed some of the research behind Simufilam to have been “fraudulent.”2 This led Schrag to Dr. Lesné’s research.
Piller writes that Schrag avoids the word “fraud” in his critiques and doesn’t claim to prove any misconduct—which would require access to original, unpublished images and raw numerical data.
“I focused on what we can see in the published images, and describe them as red flags, not final conclusions. The data should speak for itself,” Schrag stated.2
“Shockingly Blatant” Examples of Image Tampering Found
In his investigative work, Piller found that after 15 years of publications, scientists have been unable to replicate Dr. Lesné’s research findings, and few have been able to even detect the protein in human tissue.1 The Science investigation also found strong support for Schrag’s suspicions, including several top Alzheimer’s researchers reviewing Schrag’s findings and what looked like “shockingly blatant” examples of image tampering.2
According to molecular biologist and forensic image consultant Elisabeth Bik, PhD, the authors of the study “appeared to have composed figures by piecing together parts of photos from different experiments. The obtained experimental results might not have been the desired results, and that data might have been changed to… better fit a hypothesis.”2
The tampered photos being referenced are blot images used in Dr. Lesne’s research to differentiate Aβ proteins in mouse brain tissue. Several bands seem to be duplicated which was brought to Dr. Lesne’s attention by PubPeer— a website where scientists can flag possible errors in published papers. Throughout the investigation, more than 20 suspect papers were identified by Schrag or Dr. Bik.
Harvard University’s Dennis Selkoe, MD, who was a strong proponent of Dr. Lesne’s Aβ theory examined Schrag’s critiques and stated:
“There are certainly at least 12 or 15 images where I would agree that there is no other explanation” than manipulation.2
Schrag has since filed a whistleblower report to the NIH regarding Dr. Lesne’s research. He also contacted several journals which published Dr. Lesne’s work. Scrag provided his findings to Science in an attempt to speed up the process of investigation and retractions, despite knowing there may be personal consequences in doing so.
You Can’t Cheat to Cure a Disease
Schrag stated he felt an urgent need to go public about the 16 years of misdirected Alzheimer’s research. He said:
‘You can cheat to get a paper. You can cheat to get a degree. You can cheat to get a grant. You can’t cheat to cure a disease. Biology doesn’t care.”2