Alzheimer's: Falsified research calls into question 15 years of research

Alzheimer's: Falsified research calls into question 15 years of research

This is a scourge among the scientific community, in the research of Alzheimer ' s disease, as well as a kind of betrayal for all patients and their relatives. A 15-year study is based on a 2006 study whose findings have been fabricated. In subsequent years, the scientific community has tried to advance the theory advanced in this fraudulent study by a French neurobiologist from the United States of America, Sylvain Lesne, namely, that the accumulation of amyloid plaque by-product on neurons is primarily responsible for Alzheimer ' s disease. The result is a waste of time and public money for research and the collapse of patients ' hopes. Further research is needed. In any event, this study puts an end to the funding of research, which sometimes depends more on fame than on pure medical and human interests, and is obviously unfair.

In the early 2000s, several clinical trials were initiated to find a cure for Alzheimer's disease, all of which have unfortunately been unsuccessful to date. It is important to understand that Alzheimer's disease is a chronic disease that begins decades before the first signs appear and affects the most complex organ of the body — the brain.

However, research on Alzheimer ' s disease has advanced considerably over the past 15 years, and many scientific advances have been made, enabling us to better understand and diagnose Alzheimer ' s disease, better monitor its progress and identify new therapeutic targets, and these advances in research have made it possible to carry out effective prevention in order to delay the onset of the disease.

Matthew Schrag recently published a study of one of the world's most quoted studies of Alzheimer's disease, on which many therapeutic hopes are based: the hypothesis that the toxic by-products of amyloid plaques present on neurons are "most responsible" for the development of the disease. According to the Science Inquiry, the many dead ends in the research over the past 15 years are mainly related to a hypothesis that has proved to be far less reliable than we thought.

This is a study by the French neurobiologist Sylvain Lesne, who lives in the United States, published in 2006 under the auspices of the University of Minnesota, which has just begun an investigation into the researcher in connection with these allegations.

It started in August 2021, when a law firm asked Matthew Schrag, a neurologist and neurobiologist, to study the work on Simufilam, a drug against Alzheimer's, developed by the American laboratory Cassava Sciences, which is believed to improve cognitive functions through, inter alia, the repair of a squirrel philamine A, which can block deposits in the brain of a beta-amyloid protein that is typical of Alzheimer's disease. These lawyers were hired on behalf of scientists holding shares in Cassava Sciences who feared fraud in the study and then petitioned.

Matthew Schrag began a detailed review of the study that led to the development of the drug, Sylvain Lesne's research and the amiloid hypothesis, and then expanded the list of suspicious studies and found manipulation of images in dozens of articles about Alzheimer's disease.

Lesne's work and his colleagues are at the heart of a key element of the dominant but controversial amicoid hypothesis of Alzheimer's disease, according to which the main cause of the disease is the accumulation of Aβ, called fleas, in the tissues of the brain, or more specifically the by-products of these plaque, called "toxic oligomers." So they discovered the subtype Aβ and seemed to prove that it caused dementia in rats. If shraga's doubts are correct, Lesne's conclusions are a skilled mirage.

As Elizabeth Bick, a molecular biologist and a forensic visualization consultant, explains, the authors "seems to have formed figures, collecting parts of photos from different experiments." The experimental results may not have been consistent with the desired results, and these data could have been modified to better match the hypothesis, but, as Schrag reminds us in the study, "".

To highlight the manipulativeness of the results, Shrag analysed images showing level Ab*56 which, according to a 2006 study, was increasing in old mice as symptoms appeared. He found strangely similar stripes that would result in this toxic oligomer being more abundant than it really is. In particular, Shrag took a level of contrast in two sets of suspicious stripes, then turned the background black to make it easier to see, and painted them. Finally, he picked up exactly their size and orientation: it's perfect, too perfect to be manipulated. Shrag shows a clear counter-example to confirm his findings, where the differences, in this case, are seen by superposition.

By the way, Dennis Selcoe of Harvard University, the leading promoter of the theory of amyloids and toxic oligomers, said in two papers in 2008 that he could not find Ab*56 in human fluids or tissues. Selco, at the request of Science, looked into Schraga's file on Lesne's documents. He does not see manipulation in every suspicious image, but says: "A lot of other images in Lesne's articles may not be entirely appropriate — more than enough to call into question all the work, adds Selco.

The forest did not respond to requests from Science for comments or additional scientific information.

Fraud that does not call into question everyone but questions the objectivity of funding

The immediate consequence of this is obviously a waste of time and money; however, it must be understood that even if fraud is confirmed, all work should not be abandoned, much less the hypothesis on which the study was based.

One of the biggest mysteries of Alzheimer ' s disease is its most common characteristic: the pebbles and other protein sediments that the German pathologist Alois Alzheimer first saw in 1906 in the brain of a deceased patient with dementia. In 1984, Aβ was identified as the main component of the plaque, and in 1991, researchers traced Alzheimer ' s disease to the mutations in the pre-prefect ' s gene from which the amiloid was formed, and it became clear to many scientists that the accumulation of Aβ was triggering a cascade of damage and disfunction in neurons, leading to dementia.

By the early 2000s, "toxic oligomers", the Ab subtypes, which are dissolved in certain body fluids, became likely to be the main culprit of Alzheimer's disease, potentially more pathogenic than insoluble plaques. In 2006, the University of Minnesota team, including Lesne, discovered a previously unknown type of oligomer, known as Ab*56 because of a relatively high molecular weight compared to other oligomers, which, according to the authors, was largely responsible for the development of Alzheimer's disease. This study gave new impetus to stalled research and silenced doubts that had begun to arise with regard to these toxic oligomers derived from amyloid bleaches.

However, hundreds of clinical trials of anti-amyloid therapy have given only a few flashes of hope; only the disillusioning Aduelm has received the approval of the FDA. However, Aβ continues to dominate the research and development of drugs. Last year, the National Health Institutes spent about $1.6 billion on projects that mention the amiloid, which represents about half of the total funding for Alzheimer's disease. Scientists who point to other potential causes of Alzheimer's disease, such as immune dysfunction or inflammation, complain that they have been put on second ground by the "maloid mafia".

But from an objective point of view, protein Ab*56

In conclusion, in the face of such incompetent pathologies, which pose a serious public health problem, the proliferation of research areas is the only possible way to shed light on the secrets that still surround this disease, which affects more than 50 million people around the world.