Alzheimer's theory undermined by allegations of manipulated data - but does not bring dementia research to its knees

A seminal 2006 article in Nature claiming that beta-amyloid protein was the main cause of Alzheimer's was found to be partially fabricated. Long years of attempts to develop medicines were lost in vain * Twenty more articles by the same author are now being examined

The beta amyloid protein. Image: depositphotos.com
The beta amyloid protein. Image: depositphotos.com

By Mark Dallas Associate Professor of Cellular Neuroscience, University of Reading

A detective scientist has presented evidence that images used to support the claim that amyloid protein is the main protagonist in Alzheimer's disease appear to be fabricated.

It started as an investigation into an experimental Alzheimer's drug, Simufilam, but quickly snowballed into something much bigger. The investigation identified more than 20 suspect articles by the same researcher, ten of which are related to this specific protein.

The initial research paper investigated was published in 2006 in the journal Nature. Since publication, it has been cited more than 2,000 times by other scientists to support their work.

The journal is currently investigating these concerns and advised caution in interpreting the data. In addition to this 2006 paper, other research papers published by the same author have been peer-reviewed by peer scientists on PubPeer, a website that allows scientists to discuss and review scientific research after it has been published.

These discoveries call into question the scientific integrity and the role of amyloid in the pathology of Alzheimer's disease. But just how bad are these revelations?

Beta-amyloid was identified in 1984 and is now recognized as a major component of brain plaques first described by Alois Alzheimer, a German pathologist, in the early 20th century.

Beta-amyloid protein likes to aggregate into sticky clumps, and studies have shown the construction of these aggregates in impressive detail in the laboratory. The identification of this protein led to a wave of research that revealed the role that amyloid plays in the brains of people with and without Alzheimer's disease.

In 1992, this research led to the proposal of the amyloid cascade hypothesis to explain the mechanisms of disease formation: first comes the accumulation of beta-amyloid, and what follows (eg, nerve cell death) is a consequence of this process.

This hypothesis has led to the development of an array of anti-amyloid therapies that have advanced to clinical trials but have so far disappointed the Alzheimer's community.

Despite recent discoveries, it is clear that beta-amyloid does contribute to the disease - this is supported by genetic evidence. What is less clear is what other factors come together in a person's brain that lead to a diagnosis of Alzheimer's disease.

A certain type of beta-amyloid

The study in question from 2006 examined the brains of mice and reported that a particular type of the beta-amyloid protein, Aβ star 56 (Aβ*56), was at the root of the cognitive deficits seen in the mouse model of Alzheimer's disease. This has put the Aβ*56 form of the protein in the crosshairs of scientists looking for new Alzheimer's drugs.

They believed that preventing the accumulation of Aβ*56 might slow cognitive decline in people with Alzheimer's disease. However, the new report published in the journal Science suggests that the images in the original paper may have been manipulated, and the images shown were not what was reported.

The detective work revealed what appeared to be images that had been altered or reproduced to better fit the hypothesis rather than a true reflection of the experiments described in the research paper. A later study of beta-amyloid peptide in human samples failed to identify the Aβ*56 form.

These revelations may discredit a person's work, but they do not bring the Alzheimer's field to its knees.

It is true to say that the study is flawed, but the story of beta-amyloid would have developed with or without the data in question. Still, to this day scientists are trying to identify relevant levels of beta-amyloid subtypes in the blood.

Image manipulation is not uncommon

While it is disheartening as a scientist to hear about this apparent image sabotage, such behavior is not new. In 2016, a report suggested that one out of every 25 research papers has some level of image manipulation. Scientists need to do more to identify where this has happened and expose it.

New tools are available to help "detectives" uncover fraud, and journals are working hard to tackle image fraud, but there are always people who will circumvent them to present data that fits a particular hypothesis.

They do this solely to advance their careers without regard for the harm they are doing, not only to the scientific community but to people desperately seeking answers about Alzheimer's disease.

While scientists are still looking to decipher the contribution of beta-amyloid to Alzheimer's disease, several other avenues are being explored. As of January 2022, only 29% of phase 3 clinical trials (the final phase of human trials) are aimed at reducing beta-amyloid levels, therefore additional avenues are being tested that reduce some of the negative coverage associated with the research being studied.

For an article in The Conversation

More of the topic in Hayadan:

Comments

  1. Joins the reflexive gagging reaction that conspiracy theories evoke.

    And I'm embarrassed every time to read texts that haven't been proofread, and in particular "Google translations" of the type "...to identify where it happened and call it."
    The text of the riddle should be translated: "to identify where it happened and reveal it" (to call it...)

  2. A. I don't want to claim that the first commenter is a complete moron, God forbid, but it certainly seems that way.

    B. It is very, very unfortunate to hear about data falsification in science. As someone who himself has received and sent articles for peer review, indeed the tools available to the examiner are very limited and depend mainly on his sharpness and memory. It is very important to integrate artificial intelligence tools as primary filters to prevent copying and image changes. The tools exist but are not in actual use among the newspapers and peer reviewers.

  3. A study was published that claimed that increased activity of the immune system causes an increase in the rate of decomposition
    Brain cells and increasing the rate of secretion of beta amyloid beyond the ability to clear it and then it accumulates...
    Agent in every vaccine injection causes allergy and autoimmune diseases, and there are also genetically modified food plants
    Genetically produce substances that act as an adjuvant...
    For example, creating panic at the expense of a vaccine known as a "triple injection" - at the same visit they are given
    Two more injections, in each one castrated representatives of the causes of several diseases - and that's not a problem
    But with a dose of adgement in each shot - three shots = three doses of adgement.

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