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liar writes:

Two decades of Alzheimer's research may be based on deliberate fraud that has cost millions of lives

Over the last two decades, Alzheimer's drugs have been notable mostly for having a 99% failure rate in human trials. It's not unusual for drugs that are effective in vitro and in animal models to turn out to be less than successful when used in humans, but Alzheimer's has a record that makes the batting average in other areas look like Hall of Fame material.

And now we have a good idea of why. Because it looks like the original paper that established the amyloid plaque model as the foundation of Alzheimer's research over the last 16 years might not just be wrong, but a deliberate fraud.

The suspicion that something was more than a little wrong with the model that is getting almost all Alzheimer's research funding ($1.6 billion in the last year alone) began with a fight over the drug Simufilam. The drug was being pushed into trials by its manufacturer, Cassava Sciences, but a group of scientists who reviewed the drug maker's claims about Simufilam believed that it was exaggerating the potential [...] and hired an investigator to provide some support for this position.

[...] In 2006, Nature published a paper titled "A specific amyloid-β protein assembly in the brain impairs memory." Using a series of studies in mice, the paper concluded that "memory deficits in middle-aged mice" were directed caused by accumulations of a soluble substance called "Aβ*56." [...]

That 2006 paper was primarily authored by neuroscience professor Sylvain Lesné and given more weight by the name of well-respected neuroscientist Karen Ashe, both from the robust neuroscience research team at the University of Minnesota. [...]

The results of the study seemed to demonstrate the amyloids-to-Alzheimer's pipeline with a clarity that even the most casual reader could understand, and it became one of—if not the most—influential papers in all of Alzheimer's research.[...]

What intrigued Schrag when he came back to this seminal work were the images. Images in the paper that were supposed to show the relationship between memory issues and the presence of Aβ*56 appeared to have been altered. Some of them appeared to have been pieced together from multiple images. [...]

Now Science has concluded its own six-month review, during which it consulted with image experts. What they found seems to confirm Schrag's suspicions.

They concurred with his overall conclusions, which cast doubt on hundreds of images, including more than 70 in Lesné's papers. Some look like "shockingly blatant" examples of image tampering, says Donna Wilcock, an Alzheimer's expert at the University of Kentucky.

[...] And it seems highly likely that for the last 16 years, most research on Alzheimer's and most new drugs entering trials have been based on a paper that, at best, modified the results of its findings to make them appear more conclusive, and at worst is an outright fraud.

Some interesting stuff between the [...] was cut down for this summary, so I recommend reading the linked story. I also coincidentally just listened to the most recent Science podcast where they go into this in much greater detail and is well worth a listen. [hubie]

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