Leading Alzheimer’s theory undermined: Did tampering waste 16 years of research?

Sylvain Lesné's landmark 2006 study that pointed to a cause of Alzheimer's may have been doctored, calling into question whether years of research and funding were wasted.

Hundreds of millions of dollars and years of research across an entire field may have been wasted due to potentially falsified data that helped lay the foundation for the leading hypothesis of what causes Alzheimer’s disease.

The allegations centre around a landmark 2006 study — a paper which has been cited nearly 2,300 times — whose findings identify a protein called amyloid beta as a cause of Alzheimer’s. Since then, the hypothesis that sticky deposits of amyloid beta form plaques in the brain that slow cognition has dominated Alzheimer’s research and treatment development.

But a six-month investigation by Science magazine has revealed that the data backing up this influential study may have been doctored, potentially leading scientists down the wrong road for 16 years.

The controversial research was authored by Sylvain Lesné from the University of Minnesota, who at the time was a new PhD student working under the highly-regarded Alzheimer’s researcher Karen Ashe.

Lesné’s paper purported to show that a specific subtype of amyloid beta (Aβ*56) caused dementia in rats and was hailed as a major breakthrough — bringing awards, funding and notoriety to its authors, but also breathing new life into the amyloid beta theory.

In the U.S., Science found that the National Institute of Health (NIH) went from directing zero dollars for amyloid-related Alzheimer’s research in 2006, when Lesné’s research was published, to US$287 million in 2021.

A handful of scientists doubted the results of Lesné’s research but it wasn’t until 2021 when Matthew Schrag, a neuroscientist and physician from Vanderbilt University, dug deeper and found evidence that Lesné’s findings weren’t all they appeared to be.

While visiting PubPeer, a website where scientists flag possible errors in peer-reviewed research, Schrag came across postings that questioned the authenticity of some of Lesné’s graphs showing amyloid beta concentration levels. The images showed evidence of tampering and duplication, with some results seemingly cut and pasted to appear stronger.