U researchers seek to keep Alzheimer’s findings amid imaging scandal

Accusations of falsified images and manipulated Alzheimer’s research could hurt the University of Minnesota, but a bigger issue looms in the race for a cure.

U Which breakthrough discoveries in Alzheimer’s disease remain valid?

Researchers questioning whether the images from the U study have been tampered with said they could undermine a key finding in 2006. A protein called A betastar 56 is linked to rat memory. Independently causing the loss, it looked like the long-awaited smoking gun behind Alzheimer’s disease.U study leader Dr. Karen Ashe countered that colleague Sylvain Lesné was wrong to change the image. But she defended her findings.

“No edits should have been made to the selected images, but the adjustments were insignificant, trivial, and had nothing to do with the findings of the study,” she said.

An investigation by the United States and the National Institutes of Health, which funded most of the research, evaluates misconduct by Lesne or other authors, and scientific journals determine whether studies containing questionable images require revision or retraction. increase.

Behind the controversy lies a vexing neurological disease that afflicts six million Americans and is expected to increase as the population ages. This condition interferes with thought cells, neurons, the ability to perform cognitive or memory functions, or the transmission of signals that tell muscles and organs what to do.

A number of papers have questioned A study published in Nature in 2006 It has received the most attention because it discovered Abeta star 56, or Aβ*56. Some researchers have had a hard time replicating the findings, so there is little doubt about the impact of the study, but there is little doubt. It has been cited thousands of times by scientists.

Without this study and related research, “we really wouldn’t be where we are today in terms of understanding,” said Maria Carrillo, chief scientific officer of the Alzheimer’s Association. I’m here. But as the organization prepares for a convention in San Diego next week, she said: a scheduled presentation These prove that research has advanced beyond this discovery.

That said, she said it remains important to eradicate academic fraud. “We are self-regulating. If we can’t count on that, it all falls apart.”

U’s paper was based on the theory that the disease is associated with amyloid. , targeted the soluble form.

Researchers at U found a correlation between Aβ*56 and cognitive impairment in middle-aged mice genetically bred to produce amyloid plaques. The protein was then purified and injected into young rats, which resulted in memory impairment based on their inability to navigate a water maze.

At the time, the discovery that Aβ*56 impairs memory independently of plaques and neuronal loss was hailed by Nature as a ‘star suspect’ in research into a cure for Alzheimer’s disease. This paper is now tagged with a warning to treat the results with caution until the problematic images have been reviewed.

Much scrutiny is Western blotting, which uses charge to separate proteins and chemical processes to create a visual representation of them. The size and thickness of the chemical bands produced on the film correspond to the amount of protein and thus whether it is associated with disease.

Zooming in on a blot from one of the Nature papers showed bands demonstrating the presence of Aβ*56 in rats exhibiting amnesia. However, Dr. Matthew Schrag, an Alzheimer’s researcher in Tennessee, found linear discoloration around the band, suggesting it may have been cut and pasted. It looked like there was Another blot showed clusters of identical peripheral dots around the band suggesting photo editing.

Schrag announced his concerns in a review outside of his work at Vanderbilt University PubPeer Academic Website Contributed to Lesné’s Science survey in July. Expert reviewers confirmed the concerns.

“This is a very sad example of human vulnerability and cheating,” said Dr. Dennis Selcoe, a neuroscientist at Harvard Medical School. Agreed that it looks manipulated.

of chemistry The article suggests that Lesne worked with images before joining Ash’s team as a research assistant in 2002, and was promoted to assistant professor U in 2009 in his own lab. He retracted his paper before publication because he questioned the images Lesne created.

Lesné did not respond to requests for comment on this article.

U have faced this problem before and ordered a recall in 2008. groundbreaking paper About adult stem cells after discovering that they contain manipulated images.

Schrag found no research on the manipulated images that Ash was authored without Rezne, but said his concerns extend beyond the 16-year-old paper. found the signs A 2013 study published in Brain In it, researchers at U confirmed findings in human tissues regarding Aβ*56 as a precursor to Alzheimer’s disease. The revised images released this year look so different that Schlag suspects they came from the same experiment.

Blotches mean little to the untrained eye, but they’re the essence of research, says Elizabeth Bick, a San Diego microbiologist turned forensic imaging consultant. She agreed that some images in Resne’s paper appeared to be manipulated.

“A scientific paper is different from a children’s book where the images are just there to enlighten the whole story,” she said. “No. In my opinion, the images are the data.”

The now-controversial Nature paper inspired years of research. Federal funding has increased for Alzheimer’s disease in general, but for research targeting amyloid specifically.

The study was necessary because amyloid is part of the Alzheimer’s puzzle, but increased attention has delayed research on other important parts, says Ronald Petersen, director of the Mayo Clinic Alzheimer’s Research Center. says Dr. Immune responses and cardiovascular disease also play a role in Alzheimer’s disease, along with tau, a protein that can aberrantly accumulate in neurons.

The divide is showing up in drug development. Aduhelm received federal approval last year as an Alzheimer’s drug that breaks down amyloid plaques, but some doctors question whether it also slows cognitive decline. Three monoclonal antibody injections are in clinical trials. All targeted amyloid.

Trials of other compounds that target amyloid have failed. Ashe said it would be unfair to tag his controversial U papers with such failures because, unlike his Aβ*56, they contain a replication-prone class of amyloid proteins. because it was

Ash expressed doubts about whether drugs that target these proteins would work, and said she didn’t obsess over amyloid as a primary cause of Alzheimer’s disease. cause was investigated.

Carrillo of the Alzheimer’s Association said limited funding a few years ago forced a conservative decision in favor of research in areas such as amyloid where early evidence exists. The increase will encourage more daring exploration, and she hopes that Alzheimer’s treatments targeting tau and inflammation will emerge just behind the current wave of amyloid targets.

Aβ*56 is “pretty irrelevant” to current drug research, and the idea that the U controversy could undermine ongoing discoveries is “overkill and exaggerated,” she said. rice field.