Study of Alzheimer’s disease on confusion when detectives question the paper that defines the scene – Wire Science

The artist’s impression of what the inflammation of the brain from Alzheimer’s disease looks like. Illustration: NIH Image Gallery / Flickr, CC BY-NC 2.0

• 2006 study published in Nature For years, it has set the stage for research on Alzheimer’s disease, which is worth millions of dollars. The paper image may have been modified.
• The findings were guided by a study by neurologist Matthew Schrag and checked by multiple experts who agreed that the images contained signs of manipulation.
• Chemistry The journal reported its findings in a 2006 paper with a detailed report that also considered whether compounds associated with the disease actually existed.

New Delhi: The main theory of the cause of Alzheimer’s disease may have been driven by forged results and data obtained from “shockingly explicit” image tampering. Investigation To Chemistry I found.

For almost 16 years, clinical trials on how to treat Alzheimer’s disease, a neurodegenerative disease that can cause memory loss, dementia, and behavioral problems, have been influenced by a study published in a 2006 journal. I did. Nature.. It is said that the main cause of cognitive decline that is characteristic of Alzheimer’s disease is the deposition of the protein amyloid beta (Aβ) in brain tissues.

Alois Alzheimer, who first discovered the disease in 1906, found plaques and other protein deposits in the brains of deceased dementia patients. Decades later, in 1984, researchers identified Aβ as the main component of plaque.

However Nature One researcher in the group who conducted the study found that Aβ * 56, a previously unknown type of compound called an oligomer, “in the brain tissue in a study of Alzheimer’s disease that has been shown to cause memory loss. The paper was important because it claimed to be the first substance identified by. ” “

Researchers claimed to have isolated Aβ * 56 and injected it into young rats. They then wrote that the mouse’s ability to “remember simple information previously learned, such as the location of a platform hidden in a maze,” plummeted.

The findings were described as the “smoking gun” of amyloid theory and were widely appreciated.

Since publication Nature The treatise is cited in approximately 2,300 academic papers and is among the top five Alzheimer-related reports published since 2006. Chemistry..

“Since then, every year [government] Support for a study labeled “Amyloid, Oligomers, and Alzheimer’s Disease” rose from nearly zero to $ 287 million in 2021, “the magazine said.

Supporters of other potential causes of Alzheimer’s disease, such as immune dysfunction and inflammation, are “on the sidelines” as the theory becomes more predominant and receives billions of dollars from the National Institutes of Health (NIH). I did.

John Forseyes of the University of California, an expert on Alzheimer’s disease, said: Chemistry The amyloid hypothesis became the “scientific equivalent of the Ptolemy model of the solar system,” and the Earth became the center of the universe.

now, ChemistryEvidence suggests that at least 70 images published by Sylvain Lesné, a neuroscientist at the University of Minnesota, the first author of its influential 2006 paper, may have been manipulated. I found. More than 100 images related to amyloid theory are allegedly suspicious, the magazine reported.

These operations are allegedly performed to show that Aβ * 56 played a causative role in Alzheimer’s disease, but evidence may not be.

Chemistry Independent image analysts and several top researchers with Alzheimer’s disease have reviewed the findings and wrote that they agreed that the images had been tampered with.

“Some of them look like surprisingly explicit examples of image tampering.” Chemistry Donna Wilcock, an expert on Alzheimer’s disease at the University of Kentucky, said:

How was the operation identified?

In July 2021, neurologist Matthew Schrag opposed the US Food and Drug Administration’s (FDA) decision to approve a drug for the treatment of Alzheimer’s disease.The drug was based on the amyloid hypothesis, and Shrug felt that “there was little evidence that the treatment worked.” Washington post report..

“The years of study drugs targeting amyloid have caused a series of failures,” he told the newspaper at the time.

“We wanted to readjust the site,” said Schlag, a current researcher at Vanderbilt University Medical Center in Tennessee.

Shortly thereafter, Shrug was hired by a lawyer who was investigating another drug for Alzheimer’s disease, Simphyllum. The drug’s developer, Cassava Sciences, also claimed to have improved cognition by targeting amyloid deposits.

“A lawyer paid him $ 18,000 to investigate published images of the drug and its underlying science,” Shrug said of his expertise. Chemistry.. He was able to identify images that may have been modified or duplicated in dozens of journal articles.

A lawyer cliented by two neuroscientists betting that Cassaba’s stock would go down, using Shrug’s findings in a civil petition filed with the FDA to question the authenticity of the Simphyllum trial data. I threw it. Cassava shares plummeted, even though the FDA finally rejected the petition.

Schrag continued his investigation and found inconsistencies in Lesné’s work, including the important 2006. Nature paper.

He shared his findings with NIH, stating that “Dossier is part of an easily visible anomaly in the review of publicly accessible data.” Suspicious work is ” [NIH] It’s research support, but it’s been cited thousands of times, which can mislead the entire field of study, “he added.

He also gave his findings Chemistry.

A week ago, after Shrug warned Nature Regarding the possible operations in the 2006 paper, the journal Note On the page of the treatise, he states, “I was warned of concerns about some numbers.” “”Nature Is investigating these concerns and further editorial action will continue as soon as possible. In the meantime, readers are advised to be careful when using the results reported there. “

Shrug hesitated to describe Lesne’s work and cassava-related research as “fraud” or illegal activity. Chemistry To prove the fraud, he reported that he needed access to the original, completely unpublished images and raw numerical data.

“I will focus on what you can see in the published images and describe them as warning signs, not final conclusions,” he said.

Elizabeth Bick, a prominent science integrity consultant, Chemistry The author states, “It looks like a combination of photos from different experiments.”

“The results obtained may not be in line with the desired results, and these data … may have been modified to better fit the hypothesis,” she said.

Cassava denied cheating, but Lesne did not respond to a request for comment.

Karen Ashe, another senior author of the 2006 paper, was interviewed and Chemistry.. However, she posted some of the original unpublished versions of the photographs used in the 2006 paper that did not show the “digital cut marks detected by Schrag in published images.”

“This suggests that the marking was a harmless digital artifact.” Chemistry I have written. “Still, the original image reveals something that Shrug and Serkoe find even more unpleasant. Multiple bands are copied and pasted from adjacent areas, even though there are no obvious cut marks. It’s clear evidence that it was. ” Chemistry Said.

Does Aβ * 56 also exist?

moreover, Chemistry I reported that I doubted whether Aβ * 56 was present. In two papers published in 2008, Professor Dennis Serkoe of Harvard University stated that Aβ * 56 could not be found in human body fluids and tissues. There is also little independent confirmation of the Aβ * 56 claim.

“In science, after publishing data, there is a real concern that if it is not easily duplicated, it is incorrect or not true,” Serkoe said. Chemistry.. “There is little valuable clear evidence that Aβ * 56 is present or, even in animal models, correlates with Alzheimer’s disease characteristics in a reproducible manner.”

according to Hindustan TimesResearch papers published in Nature Neuroscience On June 2, he completely questioned the amyloid hypothesis. Researchers have found that mice fed with certain Alzheimer’s diseases “showed damage within neurons of the brain that occurred prior to the formation of amyloid-containing plaques.”

According to the newspaper, the paper assumed that amyloid plaques were the cause of Alzheimer’s disease, but suggested that “they may be Alzheimer’s disease.” result “In certain cases or accidental progression of the disease” (emphasis added).

However, Schrag and Selkoe said questions about the role of Aβ * 56 in Alzheimer’s disease should not question the broader amyloid hypothesis. “I hope people don’t feel weak as a result of what looks like a head-on example of the most terrible cheating in the field of Aβ oligomers,” Serkoe added.

If a phase 3 clinical trial of a drug targeting an amyloid oligomer fails, the hypothesis is “extremely threatened.”

But Serkoe also worried that “at a time of increasing skepticism and aggression, the episode of Lesne could further undermine public confidence in science.” Scientists must show that rare cases of obvious illegal activity can be found and corrected, he said.