A bombshell report casts doubt on leading Alzheimer's research

Research could have been stymied for years because of these irregularities.
Grant Currin

The current issue of Science Magazine, published by the American Association for the Advancement of Science, contains shocking allegations of scientific fraud.

The report offers evidence that one of the most important papers in Alzheimer's research — published in Nature 2006 and cited more than 2,200 times — contains images that were manipulated to make the results support a hypothesis regarding the biological basis of Alzheimer's disease. The paper suggested that a certain protein, called amyloid beta, is the main factor in causing the disease.

The paper was important because it entrenched that hypothesis as the most likely explanation for Alzheimer's — and the most important target for treatments to prevent and mitigate the disease in patients. The article in Science describes the paper as a “smoking gun” in support of the hypothesis.

James Giordano, Professor of Neurology, Biochemistry and Ethics at Georgetown University Medical Center, tells IE these papers underpin an excessive focus on the hypothesis that has prevented money from funding other streams of research that could have led to effective therapeutics. “To me, that is extremely problematic,” he says.

The report casts doubts on Alzheimer's research.
The report casts doubts on Alzheimer's research. haydenbird/iStock

Studies with “red flags” have been extremely influential

These allegations are extremely important because the papers he flagged have elevated the amyloid beta hypothesis from a controversial idea to standard thinking among in Alzheimer's research. In the current fiscal year, the NIH spent roughly half its funding for Alzheimer's research — $1.6 billion — on projects that mention the protein. 

Nobel laureate and Alzheimer's researcher Thomas Südhof told Science, “[t]he immediate, obvious damage is wasted NIH funding and wasted thinking in the field because people are using these results as a starting point for their own experiments.”

Giordano agrees, telling IE the focus on the amyloid beta hypothesis “as diverted money away from other domains... [that could] elucidate other viable targets which could then be valuable for both diagnosis as well as intervention.”

He says this episode shows that “science does not occur to social vacuum, and that there is a culture within science.” While it's tempting to think that institutions like peer review are “oriented towards mitigating or preventing bias,” they can, in practice, reinforce popular hypothesis at the expense of new ideas. 

“The problem with locking onto a single hypothesis — and then essentially fortifying the hypothesis over and over again to the exclusion of others — is that you lock in that type of thinking, and you tend to be exclusionary to other possibilities,” he says.

“That's what's important.”

In the case of Alzheimer's, many competing hypotheses “involve amyloid to some extent, [but] do not necessarily indicate amyloid exclusively,” he says.

Questions about a new drug found deeper problems in the field

Nearly a year ago, a colleague asked neuroscientist and physician Matthew Schrag to take a look at some research papers that drug company Cassava Science used to win FDA approval for an Alzheimer's drug called Simufilam. “He identified apparently altered or duplicated images in dozens of journal articles,” Science reports.

But that isn't the most important irregularity (Schrag avoids the word “fraud”) the researcher found. Schrag identified similar problems with the 2006 Nature paper and several others by the same researchers. He reported what he knew to the relevant journals and to the National Institutes of Health, which is a government agency responsible for funding a large percentage of biomedical research in the United States. Then, he contacted journalists at Science, which spent six months investigating the claims and found “strong support for Schrag’s suspicions,” according to the article.

The issues could call into question the allocation of research funds and lead to a reassessment of research focus.

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