Scandal surrounds 2006 article, keystone of recent dementia work, that critics say is based on ‘shockingly blatant’ evidence tampering
The key theory of what causes Alzheimer’s disease may be based on ‘manipulated’ data which has misdirected dementia research for 16 years – potentially wasting billions of pounds – a major investigation suggests.
A six-month probe by the journal Science reported “shockingly blatant” evidence of result tampering in a seminal research paper which proposed Alzheimer’s is triggered by a build-up of amyloid beta plaques in the brain.
In the 2006 article from the University of Minnesota, published in the journal Nature, scientists claimed to have discovered a type of amyloid beta which brought on dementia when injected into young rats.
It was the first substance ever identified in brain tissue which could cause memory impairment, and seemed like a smoking gun.
The Nature paper became one of the most-cited scientific articles on Alzheimer’s ever published, sparking a huge jump in global funding for research into drugs to clear away the plaques.
But the Science investigation claims to have found evidence that images of amyloid beta in mice had been doctored, in allegations branded “extremely serious” by the charity Alzheimer’s Research UK.
Elizabeth Bik, a forensic image consultant, brought in to assess the images, told Science that the authors appeared to have pieced together parts of photos from different experiments.
“The obtained experimental results might not have been the desired results and that data might have been changed to … better fit a hypothesis,” she said.
‘Mislead an entire field of research’
Issues with the research were originally spotted by neuroscientist Dr Matthew Schrag of Vanderbilt University, Tennessee, who noticed anomalies while involved in a separate investigation into an experimental Alzheimer’s drug.
In a whistleblower report to the US National Institutes of Health (NIH), Dr Schrag warned that the research “has the potential to mislead an entire field of research”.
The journal Science looked separately into his claims, and said its own investigation “provided strong support for Schrag’s suspicions”.
Although the Minnesota authors stand by their research, the claims are now being studied by the NIH, who can choose to pass on the matter to the US Government’s Office of Research Integrity if deemed to be credible.
The journal Nature has also launched its own investigation and has placed a warning on the 2006 article urging readers to “use caution” when using the results.
If proven, such manipulation could mark one of the biggest scientific scandals since Dr Andrew Wakefield linked the MMR jab to autism in a 1988 Lancet article.
Plaques in the brain were first identified in dementia patients by the German psychiatrist Alois Alzheimer in 1906, and in 1984 amyloid beta was found to be their main component.
For the next 20 years, hundreds of trials were conducted into therapies targeting amyloid in the brain, but all failed, leading to the theory being largely abandoned until the Minnesota paper was published in 2006.
Since then, universities, research institutions and pharmaceutical companies have spent billions investigating and trialling therapies to clear the brain of amyloid, but none have worked.
Dennis Selkoe, professor of neurologic diseases, at Harvard University, told Science that there was “precious little evidence” that the amyloid found by the Minnesota team even existed.
Professor Thomas Sudhof, a Nobel laureate of Stanford University, added: “The 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.”
The authors of the Minnesota paper have defended their original findings claiming they “still have faith” that amyloid play a major causative role in Alzheimer’s.
Amyloid itself not in question
Commenting on the findings, Dr Sara Imarisio, head of research at Alzheimer’s Research UK, said: “These allegations are extremely serious. While we haven’t seen all of the published findings that have been called into question, any allegation of scientific misconduct needs to be investigated and dealt with where appropriate.
“Researchers need to be able to have confidence in the findings of their peers, so they can continue to make progress for people affected by diseases like dementia.
“The amyloid protein is at the centre of the most influential theory of how Alzheimer’s disease develops in the brain. But the research that has been called into question is focused on a very specific type of amyloid, and these allegations do not compromise the vast majority of knowledge built up during decades of research into the role of this protein in the disease.”
Dr Richard Oakley, associate director of research at Alzheimer’s Society, said: “There are many types of amyloid we know contribute to brain cell death in dementia. If what’s suggested here ends up being true we definitely would not need to throw the baby out with the bath water.”