Senior U scientist responds to allegations of fraud in Alzheimer’s disease research

A top University of Minnesota scientist said it was ‘devastating’ that a colleague could doctor images to support the research, but she defended the authenticity of her groundbreaking work on the origins of the disease. Alzheimer’s disease.

Dr. Karen Ashe declined to comment on a U investigation into the veracity of studies conducted by Sylvain Lesné, a neuroscientist she hired and a rising star in the field of Alzheimer’s disease research. However, she criticized an article in Science magazine which raised concerns this week about Lesné, as she said he confused and exaggerated the effect of the U’s work on downstream drug development to treat dementia related to Alzheimer’s disease.

“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 colleague may have misled me and the community. scientist, tampering with images,” Ashe said. in an email Friday morning. “However, it is also distressing that a major scientific journal has blatantly misrepresented the implications of my work.”

Questions have surfaced over no less than 10 papers written by Lesné, and often co-authored by Ashe and other U scientists, and whether they used manipulated or duplicated images to inflate the role of a protein 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 and magnified the images of Lesné’s studies in ways that revealed questions about whether they were doctored or copied. Expert consultants agreed in the article that some of the images from the U studies appeared to be manipulated to increase the importance of a protein called Aβ*56.

Many of the images were Western blot tests showing that Aβ*56, also called amyloid beta star 56, was more prevalent in older mice and showed signs of memory loss.

The U-studies have had such an influence on the course of Alzheimer’s disease research over the past two decades that any evidence of manipulation or false study results could fundamentally alter thinking about the causes of the disease and dementia. The survey also involves two researchers who have succeeded on a key measure by which they are judged: their ability to attract federal grants.

Lesné was named the recipient of $774,000 in grants from the National Institutes of Health specifically involving Aβ*56 from 2008 to 2012. He subsequently received over $7 million in additional NIH grants related to the origins of Alzheimer’s disease .

Lesne, who did not respond to an email seeking comment, came to U in 2002 as a postdoctoral research associate after completing his doctorate at the University of Caen Normandy. He took charge of his own U lab in 2009 and became associate director of graduate studies for the neuroscience program in 2020. He was the first or last author of all of the disputed studies, meaning he either initiated the research or was the principal investigator supervising the work.

Ashe said there are two classes of Aβ proteins, which she calls Abeta, and her efforts have focused on one while drugmakers have unsuccessfully targeted the other with potential treatments for the disease. of Alzheimer’s. As a result, she said it was unfair that the Science article – even though it raised concerns about research irregularities – singled out an entire industry’s lack of progress on the research U reviewed.

“It’s the latter form that drug developers have targeted repeatedly but without success,” she said. “There have been no clinical trials targeting the type 1 form of Abeta, the form my research suggested is more relevant for dementia. [The article] mistakenly confused the two forms of Abeta.”

The scientific journal Nature reviews a 2006 study led by Lesné regarding the existence and role of Aβ*56 and urges people to use it with caution for now. Concerns have arisen in part because researchers at other institutions have struggled to replicate the results.

Two other papers from 2012 and 2013 were corrected earlier this year, with the U researchers acknowledging the erroneous images but saying they did not affect the overall conclusions. However, Schrag said he was concerned that the corrected images had also been manipulated.

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

Beneath the research controversy lies fundamental research and debate about the causes of Alzheimer’s disease and related dementias. One theory is that certain Abeta proteins lead to the development of amyloid plaques, which clog the space between nerve cells in the brain and inhibit memory and cognition. Another is that tau proteins clump together inside brain thinking cells and disrupt them.

Ashe’s research explored both possibilities. Since 1986, she has been named the recipient of more than $28 million in NIH grants, making her one of the most productive researchers in the history of the University.

Complicated inheritance

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

The late Dr. S. Charles Schulz resigned as U psychiatry chair in 2015 amid claims from a grieving family that their son, who died by suicide, had been coercively recruited into a trial on a drug for schizophrenia.

Duplicate images and errors forced the correction of a 2002 Nature study, led by Dr. Catherine Verfaillie, claiming that some adult stem cells possessed flexible abilities to grow and develop other cell types.

The late Dr. John Najarian was an organ transplant pioneer who raised the U’s global profile, but he faced federal sanctions in the 1990s related to the illicit sale of an anti-rejection drug experimental drug that improved transplant outcomes.

The UA’s investigation into Lesné’s work will follow its standard research misconduct allegations policy, according to a statement from the medical school.

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