Report says key elements of influential Alzheimer’s study may have been fabricated

What did the science article say?

It reported that key items in the Nature paper, whose lead author was Sylvain Lesne, a neuroscientist at the University of Minnesota School of Medicine, contained manipulated data images. It is under investigation by the university and has not responded to requests from Science for comment.

Why was the study of nature important?

She investigated cognitive decline in mice and hypothesized that a specific beta-amyloid protein, called Aβ*56, might be responsible for the disease. Matthew Schrag, a neuroscientist and physician at Vanderbilt University, analyzed images from a 2006 research paper and found signs that the results of the experiments may have been fabricated, according to a scientific article published last week. Schrag avoided using the word “fraud” in his criticism. “I focus on what we can see in the posted images, and describe them as red flags, not final conclusions,” he said. He said in science.

What is the relationship of amyloid to Alzheimer’s disease?

For years, researchers have known that the sticky protein often clumps into plaques in the brains of people with the disease. However, scientists continue to debate whether amyloid causes Alzheimer’s disease or if it is just a byproduct of the disease. Aduhelm, Biogen’s monoclonal antibody approved by the Food and Drug Administration last year, targeted the amyloid protein but a different form of the protein than Lesné targeted. Scientists say there are dozens of different forms.

If the Nature paper contains fabricated data, does that eliminate the amyloid hypothesis?

Not necessarily, according to some scholars. “This was kind of a prevalent hypothesis and still is, and it was not based on any single publication, although admittedly [the 2006 paper] “It is never a good idea to have a science fabrication,” said Charles Glabe, professor of molecular biology and biochemistry at the University of California, Irvine. “Glabe was listed as a co-author on the Lesné paper because his lab provided one of the antibodies used in the research.” Everyone gives black eyes, and unfortunately that happens more often than we think.”

Dennis Silko, MD, co-director of the Ann Romney Center for Neurological Diseases at Brigham and Women’s Hospital, posted on the Alzforurm.org website that “it’s not a scientific setback at all” because several other research papers have suggested that amyloid proteins may cause Alzheimer’s disease. “Rare examples of wrongdoing and fraud occur in all areas of human endeavour, and I do not feel that Sylvain Lesny’s actions are a reflection of AD research over the past four decades,” Silko said in an email.

Rudolph Tanzi, MD, deputy chief of neurology at Massachusetts General Hospital, said he still believes targeting amyloid plaques is one of the best hopes for Alzheimer’s patients. “It actually had very little impact on the amyloid hypothesis or the direction of Alzheimer’s disease research,” he said in a 2006 paper in an email, “because within two years, scientists were unable to replicate the findings.”

But other scientists have long felt the researchers focused too much on amyloid and said the scientific investigation only supported their view.

“For many of us, this is not surprising,” Brian Silver, interim chief of the neurology division at UMass Memorial Health, said in an email. The amyloid hypothesis has been challenged for at least a decade. While amyloid buildup may be necessary for the disease to occur, it is not sufficient alone. Autopsy studies show patients with significant accumulation of amyloid and no evidence of dementia during life. The current thinking is that another protein (tau) may actually be the driver of disease progression.”

What might break the amyloid hypothesis?

Biogen, Roche and Eli Lilly and Company are testing three other experimental drugs that target amyloid in late-stage clinical trials, with results expected in the coming months. If all of these drugs fail, the hypothesis is “largely under duress,” Silko said in Science.

What makes Biogen a science article?

A company spokeswoman said Biogen had no comment. Dominic Walsh, head of Biogen’s Alzheimer’s Disease and Dementia Research Unit, said on Alzforum.org that the allegations were “disturbing and distressing” but “have very few implications for the amyloid hypothesis.” He wrote that the results of the upcoming trial will issue the most important ruling.


Jonathan Saltzman can be reached at [email protected] Ryan Cross can be reached at [email protected] Follow him on Twitter Tweet embed.

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