Key Alzheimer’s papers may have been fabricated

(ORDO NEWS) — The leading scientific journal Science writes that a hugely influential 2006 article and a number of related papers that have greatly influenced Alzheimer’s research and became the basis for the search for treatments contain numerous falsifications.

The motivation for the fake is considered to be the personal interests of supporters of one of the hypotheses of the pathogenesis of neurodegeneration – the authors call them the “amyloid mafia”.

Alzheimer’s disease is the most common neurodegenerative disease with increasing social significance. It affects tens of millions of people around the world, forecasts predict a rapid increase in their number, and there are still no effective methods of therapy.

And this is against the backdrop of colossal financial resources, which are always willingly provided for work in this area.

The state of affairs makes one think that such research, if not deadlocked, is in crisis. It looks like one of the articles in the July issue of Science explains the situation, although it does not apply to scientific publications.

It describes the proceedings around the 2006 Nature article “A specific amyloid-β protein assembly in the brain impairs memory”. Its first author was Sylvain Lesne, a neuroscientist at the University of Minnesota (USA), at the time a rising star among Alzheimer’s researchers.

The article describes a specific variety of beta-amyloid , a small peptide considered important in pathogenesis, Aβ*56. This is a relatively large oligomeric form of beta-amyloid, one of many known. Lesne and colleagues argued that Aβ*56 is critical for the development of neurodegeneration.

In the article, they describe that the introduction of this form of the peptide into the brains of young rats impairs memory and learning, and the results looked convincing.

Since 2006, this article has been cited in more than 2200 scientific publications, followed by a number of related papers received and spent grants. For more than a decade, Lesne’s article has influenced modern thinking about Alzheimer’s disease.

However, questions surrounding a recently proposed new drug for Alzheimer’s disease (simufilam) have generated a lot of controversy.

An important role in it was played by Matthew Schrag from Vanderbilt University (USA), who became a kind of debunker for Lesne and his supporters. World-renowned Alzheimer’s authorities including Dennis Selkoe are also participating.

They uncovered numerous forgeries of images used in scientific papers. We are talking about hundreds (!) images: there are more than 70 of them in Lesnay’s works alone, including those illustrating the results of a Western blot , a technique that allows you to identify protein molecules. More than 20 publications of the scientist are under question, including ten related to Aβ*56.

An analysis of the set of raised initial data and a survey of the authors showed that the pictures were edited, including swapping parts of them. Obviously, getting results that did not correspond to their hypotheses and interests, the researchers quite literally “drawn” in their place those that they liked more.

The effect of this (in fact, the damage) is difficult to assess. Hundreds of millions of dollars have been spent on fundamental research and the search for drugs in line with these works.

It appears that it is in large part because of Lesne’s article and related publications that this extremely important area of ​​biomedical research has “taken the wrong turn” by continuing to defend and promote the amyloid cascade hypothesis.

The development of Alzheimer’s disease is a complex, time-consuming process that occurs with the participation of many molecules and cellular structures.

The oldest hypothesis of pathogenesis is amyloid: it originates from Alois Alzheimer’s description of plaques in the brain of the first patient more than a century ago.

The hypothesis poorly explains what is happening in the brains of patients, and most importantly, it did not allow the development of an adequate therapy, despite decades of effort and huge funding, which continued to disappear like a black hole.

At the beginning of the new millennium, the amyloid cascade hypothesis was subjected to active criticism, but survived – including thanks to the results of Lesnay and the personal interest of people, nicknamed in Science “the amyloid mafia.”

Previously, these unflattering events have deprived support of other hypotheses of the pathogenesis of Alzheimer’s disease, paying more attention to the tau protein , the prion properties of proteins, the role of immunity, iron and calcium homeostasis, and so on. In many ways, they also explain the failure of the search for drugs: for the treatment of this neurodegeneration, only a few drugs with very limited efficacy are still approved .

At the same time, the situation allows us to hope that the approach of researchers to this problem may finally begin to change.

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