For more than 15 years, the global scientific community researching Alzheimer’s Disease has focused its attention—and hundreds of millions of research dollars—on the theory that the disease is primarily caused by the build-up of plaque, called amyloid beta, in the brain. But what if that theory is based on flawed data?
A six-month investigation by Charles Piller, an award-winning reporter for Science magazine, finds that key research published in 2006 may have included fabricated data. The 2006 breakthrough study, published in the journal Nature, identified a subtype of amyloid called amyloid beta star 56 (Aβ*56) as the cause of memory loss in mice.
The controversial research was published by Sylvain Lesné of the University of Minnesota. For years, a handful of scientists questioned Lesné’s results but few paid close attention. In 2021, Matthew Schrag, a neuroscientist and physician at Vanderbilt University, was hired by a lawyer representing two “short-seller” investors to investigate claims by a maker of an experimental Alzheimer’s drug. That led him to dig into Lesné’s original research.
The problem is...Lesné’s work is one of the most cited scientific articles on Alzheimer’s ever published. That paper has been cited nearly 2,300 times, indicating the sheer number of scientists that spent time focusing their own work on this theory.
This single study led to billions of dollars in funding and a major research effort to find a treatment that would sweep the damaging protein from the brain.
While Schrag did not accuse the researcher of misconduct, the evidence that data were manipulated appears strong. In his investigation, Piller found scientists have been unable to replicate Lesné’s work, a critical step in all research. Indeed, after 15 years, few have been able to even detect Aβ*56 in human tissue.
Accusations Of Doctored Images
Lesné’s paper in question employed a well-known and commonly used technique called western blots to detect proteins in blood or tissue. The findings are presented as photographic images. The investigation claims there’s “shockingly blatant” evidence the images used were manipulated.
In fact, Dr. Elisabeth Bik, a research fraud expert who reviewed the images, explained, saying, “Manipulating images like these is simple to do with Photoshop. You can edit out parts you don’t want. Both of these things appear to have been done in this case.”
Dennis Selkoe, professor of neurologic diseases at Harvard University, said there was “precious little evidence” the amyloid the researchers claimed to have found even existed.
Meanwhile, Richard Smith, former editor-in-chief of the British Medical Journal said he wasn’t surprised. He’s been concerned about research fraud in the medical field for 40 years. He wrote last year: “We have now reached a point where those doing systematic reviews must start by assuming that a study is fraudulent until they can have some evidence to the contrary.”
Unfortunately, the University of Minnesota paper isn’t the only example to rock the field of dementia research.
The dementia drug simufilam, produced by Cassava Sciences, looked promising. Trial data showed it could slow and might even reverse cognitive decline in Alzheimer’s patients.
But the scientists involved have encountered allegations of data manipulation and misrepresentation, the use of questionable methods of analysis, numerous methodological errors, and trial results that were "overblown, inappropriate, and uninterpretable." Not surprisingly, one of the study authors has had five other papers retracted because of “serious concerns about the integrity and reliability of the results.”
What’s more, Cassava Sciences is now being investigated by the U.S. Department of Justice to see whether investors and government agencies have been defrauded.
FDA Members Resigned Over This Drug
Another dementia drug that I wrote about a few months ago, aducanumab (Aduhelm), hit the headlines last year when it became the first new Alzheimer’s drug to be approved by the FDA in 20 years. But its usefulness has been disputed by scientists, including three members of the FDA’s own advisory committee who resigned in protest of its approval.
Robert Howard, Professor of Old Age Psychiatry at University College London, was dismayed by the FDA’s decision. “I consider the approval of Aduhelm represents a grave error that will have only negative impact on patients and their families and that could derail the ongoing search for meaningful dementia treatments for a decade. Amazingly, the FDA have sidestepped available clinical trial outcomes data that indicate the drug probably doesn’t work.”
What Can Be Done?
Richard Smith believes scientific journals should be held accountable and fined if they publish fraudulent research and don’t correct it swiftly. He also supports criminal prosecutions against scientists who carry out such research.
Dr. Bik agrees that publishers need to take responsibility and suffer penalties, otherwise nothing will change. "Until we hold them accountable, it will be the public that suffers the consequences of fraud.”
The Science investigation, following so many failed amyloid beta drug trials, suggests a colossal scientific failure that may have led to needless suffering by those living with Alzheimer’s Disease and their family members.
As a practicing Scientist myself...I know that the overwhelming majority of scientists are doing the right thing all of the time and are committed to bettering their respective fields and advancing research & development. If regulatory approval authorities such as the FDA and Health Canada continue to sensibly and thoroughly examine the evidence provided for approval, then we can hope for a better future for people living with Alzheimer’s.