Senior U Scientist Responds to Allegations of Fraud in Alzheimer’s Research

A prominent scientist at the University of Minnesota said it was “devastating” that a colleague had manipulated the images to support the research, but she defended the credibility of her groundbreaking work on the origins of Alzheimer’s disease.

Dr. Karen Ash declined to comment on Yu’s investigation into the validity of studies led by Sylvain Lesne, the neuroscientist she hired and a rising star in Alzheimer’s research. However, it criticized an article in Science that raised concerns this week about Lesny, because it said it confounded and exaggerated the impact of U’s work on developing downstream drugs to treat Alzheimer’s-related dementia.

“Having worked for decades to understand the cause of Alzheimer’s disease, so that better treatments can be found for patients, it is devastating to discover that a co-worker may have misled me and the scientific community through image manipulation,” Ash said. In a letter on Friday morning. “However, it is also sad to find a major scientific journal has grossly misrepresented the implications for my work.”

Questions arose about as many as 10 research papers written by Lesny, often co-authored by Ash and other scientists at Yu University, and whether they used manipulated or duplicate images to amplify the protein’s role in the onset of Alzheimer’s disease.

The Science article detailed the efforts of Dr. Matthew Schrag, an Alzheimer’s researcher in Tennessee, who colorized images from Lisney’s studies and amplified them in ways that revealed questions about whether they had been manipulated or copied. The consultants in the article agreed that some of the images in the U studies appeared to have been manipulated in ways that increase the importance of a protein called Aβ*56.

Several images of western blot tests were showing that Aβ*56, also known as amyloid beta star 56, was more prevalent in older mice and showed signs of amnesia.

The U studies have been so influential on the course of Alzheimer’s disease research over the past two decades that any evidence of manipulation or erroneous study results can fundamentally change thinking about the causes of disease and dementia. The investigation also suggests that successful researchers are implicated in a key metric by which they are judged: their ability to attract federal grants.

Lesné received $774,000 in NIH grants that specifically include Aβ*56 from 2008 through 2012. He subsequently received more than $7 million in additional NIH grants related to the origins of Alzheimer’s disease.

Lesnee, who did not respond to an email requesting comment, came to U in 2002 as a postdoctoral research associate after receiving his doctorate from the University of Caen, Normandy. He took charge of his U lab by 2009 and became associate director of graduate studies in the neuroscience program in 2020. He was the first or last author on all of the disputed studies, meaning he either instigated the research or was the chief scientist supervising the work.

Ash said there are two classes of Aβ proteins, which she refers to as Abeta, and that her efforts have focused on one while other drug companies have unsuccessfully targeted with potential treatments for Alzheimer’s disease. As a result, she said, it was unfair in the Science article – even as it raised concerns about research errors – to demonstrate the entire industry’s lack of progress in the U’s examined research.

“This is the last form that drug developers have repeatedly targeted but to no avail,” she said. “There have been no clinical trials targeting type 1 ABETA, which is the form that my research has suggested is more relevant to dementia. [The article] He wrongly mixed the two forms of Abeta.”

The scientific journal Nature reviews a 2006 study led by Lesny regarding the presence and role of Aβ*56 and urges people to use it with caution at this time. The concerns arose in part because researchers at other institutions have struggled to replicate the findings.

Two other papers were corrected in 2012 and 2013 earlier this year, with U researchers acknowledging the existence of false images but stating that they did not affect the overall conclusions. However, Schrag said he has concerns about manipulating the corrected images as well.

“I think these corrected images are very problematic,” he said.

Beneath the research controversy there is primary research and debate on the causes of Alzheimer’s disease and associated dementia. One theory is that certain Abeta proteins lead to the formation of amyloid plaques, which fill the space between neurons in the brain and dampen memory and cognition. Another reason is that tau proteins clump inside the brain’s thinking cells and disrupt them.

Ash’s research explored both possibilities. Since 1986, she has received more than $28 million in NIH grants, making her one of the most productive researchers in U.S. history.

complex legacy

Despite the remarkable history of life-saving inventions and surgical achievements, U also has a legacy of research stars embroiled in scandals.

The late Dr. S. Charles Schulz resigned from his position as chief psychiatrist in 2015 amid allegations from a grieving family that their son, who had committed suicide, had been forcibly recruited into a drug trial for schizophrenia.

Duplicate images and errors forced a correction in a 2002 Nature study led by Dr. Catherine Verfaili, claiming that some adult stem cells have the flexible capabilities to grow and develop other types of cells.

A pioneer in organ transplantation, the late Dr. John Najarian raised U’s global profile, but faced federal sanctions in the 1990s related to illegal sales of an experimental anti-rejection drug that improved transplant outcomes.

According to a statement from the medical school, the African Union’s investigation into Lisnei’s work will follow its standard policy on allegations of research misconduct.

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