We are republishing this article from Science Media Center Spain published on June 26, 2022.
The magazine Science published a report revealing multiple signs of fraud in one of the most cited publications on Alzheimer’s disease. We explain what this means for the science that studies this disease.
A publication in the magazine Science uncovered a possible case of fraud in a major line of investigation against the Alzheimer’s. The alarm signal made it sound Matthew Slantwiseneurologist and neuroscientist at Vanderbilt University (USA), there the magazine itself continued the analysis. Specifically, they identified that there was every kind of image manipulations in at least say articles on the call peptide Ab*56. All bore the signature of neuroscientist Sylvain Forest.
The Ab*56 is a way to enter which can be presented beta-amyloid protein (also written as β-amyloid), the substance found plaques forming in the brains of sufferers Alzheimer’s and which, according to the dominant theory in recent decades, is responsible for the initiation of the disease.
One of these ten articles is one of the most cited in the history of Alzheimer’s disease research. Published in the magazine Nature in 2006assured that when injecting the form Ab*56 in healthy rats, these developed memory leaks. It was the first time that showed that a substance, theoretically present in the brains of people with Alzheimer’s disease, Alzheimer’sdirectly caused these symptoms. It was a boost for the hypothesis amyloid.
Slantwise he avoids the term “fraud” in his criticisms and describes his findings as a “red flag”. Other experts consulted by the magazine Science they describe them as “striking examples of image manipulation”. It is also said that many other groups unsuccessfully tried to reproduce the resultsbut very few reported it. Although a non-repeatable result does not necessarily imply fraud, the article acknowledges that exist very little interest in negative results and it is difficult to contradict authoritative researchers.
Following the post, some items there several comments in social networks they claimed that the whole investigation into the Alzheimer’s was based on fraud and that they had been squandered hundreds of millions of euros and decades of effort. However, many experts have attempted to refute these findings and contextualize its repercussions. everything turns around the protein beta-amyloid.
What is β-amyloid
These are small fragments that come from the so-called amyloid precursor protein. There are many different forms that tend to aggregate and eventually form the characteristic plaques of Alzheimer’s disease. In the case of Ab*56this would be called a soluble oligomer, serious a presumably toxic but untraceable form being part of the plates.
This is a simple timeline of some important discoveries:
- between 1906 in 1911, Alois Alzheimer (and Oskar Fischer) begin to describe patients’ characteristic plaques.
- In 1984, it was established that the protein b-amyloid is the main component plates.
- in 1991 start to be published that several mutations that increase the amount of amyloid precursor protein inevitably cause disease in those who carry them. It is assumed to be the cause of Alzheimer’s disease and the theory is becoming mainstream.
Does the possible fraud dismantle the theory of amyloid and Alzheimer’s disease?
No. In words a twitter of the researcher Alzheimer’s Charles herrup“The scale of the fraud is shocking, but the importance to the field of Alzheimer’s disease was seriously exaggerated”. According the chemist Derek Lowe, ex-investigator from Alzheimer’s and responsible for a blog in magazine Science“vsIt certainly increased enthusiasm and funding levels in the region and gave people more reason to believe.”. However, work on Ab*56 now in question”I did not driveiran directly to any clinical trial on this concrete form”. Surely too many eggs were put in the same amyloid basket, but it was not caused by these elements.
These works were a boost, but they are only a branch in the whole tree of the theory. Also on Twitter, the inspector Samuel Marais explained that “eThe main job in question Nope established the amyloid plaque model. He was talking about a specific oligomer called AB*56. There are many other articles in this area showing the importance and effects of oligomers and plates”. And he continued:I sincerely doubt that the absence of this particular item and AB*56 from the historical scientific record would havenot has dramatically changed the last 20 years of drug development for Alzheimer’s disease. Indeed, there is strong genetic and other evidence for the role of amyloid in the disease.”.
By John Hardydiscoverer of one of the mutations that inevitably lead to disease, “andIt’s a shame that these works involve deception, and that journals and institutions should take action against fraud when discovered.and”. However, “never I thought this article important, and I think I never referred to it in my own work.”.
The amyloid theory was already controversial before this case. Because?
In recent years there has been a Intense debate over the relevance of amyloid in Alzheimer’s disease. One of the reasons is that many older people have plaques amyloid, but i have no symptoms, so He is this might not be enough to develop the disease. On the other hand, and this is the main reason, although clinical trials aimed at reducing plaques have repeatedly succeeded in reducing them, they have invariably failed. on time to improve symptoms. even those trials done early there in people with mutations who has themdinner in the future develop the diseaseD they did not show no improvement.
Currently there is only one drug antiamiloideo approved for Alzheimer’s aducanumab. Se gave him the green light in the United States in the midst of a huge controversyboth for the weird development of clinical trials in accordance with the final decision. In Europe, the European Medicines Agencyoh refused to approve italluding to the fact that it had not shown clinical benefit and was not safe enough.
What could explain the failure of clinical trials
Some of the explanations considered are:
- Although by logic and by genetic studies it is difficult to accept, it is possible that the amyloid is what is called a epiphenomenon, something that accompanies the true cause but does not actue As such.
- It could be that the treatments included in attempts they were not arriving on time. Amyloid damage could be very early, and reducing it once it has triggered the aggression may not be enough. Although some trials have been carried out on people still without symptoms, it may still be too late.
- Another option is that the antibody used to decrease amyloid they didn’t reduce it enough or that they acted against certain forms of what were most toxic. In this case yese would reduce the total quantity, but not what it produces really the damage.
And it is increasingly recognized that Alzheimer’s disease is a syndrome, rather than an unequivocal disease, and that there are many factors to consider.
About this particular casethus ended his explanation Samuel Marais: “Good, That’s all for the moment. Horrible behavior, yes. The reason why the domain of Alzheimer’s disease focused on amyloid for 16 years: absolutely not. It is Ta it’s a great news in itselfbut the hyperbolic information and not very precise make things worse”.