The data behind the most influential theory on the causes of Alzheimer’s disease may have been “manipulated”, according to a damning scientific investigation.
Experts fear the allegedly falsified results have misled research over the past 16 years, potentially wasting billions of pounds in funding.
A six-month investigation by Science, considered one of the world’s most respected research journals, revealed “shocking and gross” falsification of results in the landmark 2006 study from the University of Minnesota.
The paper pointed to a particular protein – known as beta-amyloid – as a driver of Alzheimer’s disease. It was the first substance in brain tissue ever identified that appeared to cause the disease’s memory-stealing effects.
Published in the rival journal Nature, the study became one of the most cited papers on Alzheimer’s disease ever published.
About £1.3 billion ($1.6 billion) in funding for studies mentioning amyloid was spent by the US government in the last year alone. It accounted for half of the country’s total funding for Alzheimer’s disease research.
But the images from the study, which involved injecting the protein into mice, appear to have been doctored to “better fit a hypothesis”, according to Dr Elisabeth Bik, a forensic image consultant who was asked to comment. examine the data.
Charities today slammed the ‘extremely serious’ allegations.
But they insisted the theory itself still holds because decades of research have identified other amyloid proteins as to blame. Even if the original results were tampered with, a top expert claimed that “we certainly wouldn’t need to throw the baby out with the bathwater.”
The most influential theory about the causes of Alzheimer’s disease that has sparked hundreds of trials may have been based on ‘manipulated’ data, it has emerged
WHAT IS ALZHEIMER’S DISEASE?
Alzheimer’s disease is a progressive and degenerative disease of the brain, in which the accumulation of abnormal proteins leads to the death of nerve cells.
This disrupts the transmitters that carry the messages and causes the brain to shrink.
More than 5 million people suffer from the disease in the United States, where it is the sixth leading cause of death, and more than a million Britons have it.
When brain cells die, the functions they perform are lost.
This includes memory, orientation, and the ability to think and reason.
The progression of the disease is slow and progressive.
On average, patients live five to seven years after diagnosis, but some may live ten to 15 years.
- Short term memory loss
- Behavioral changes
- Mood swings
- Difficulties managing money or making a phone call
- Severe memory loss, forgetting close family members, familiar objects or places
- Become anxious and frustrated with the inability to make sense of the world, leading to aggressive behavior
- Eventually loses the ability to walk
- May have problems eating
- The majority will eventually need round-the-clock care
Source: Alzheimer Association
Dr. Matthew Schrag, a neuroscientist at Vanderbilty University in Tennessee, was the first to discover problems with the Nature study.
He noticed anomalies in the original images, released by Dr. Sylvain Lesné and his team, during another investigation into an experimental drug for Alzheimer’s disease.
They had “the potential to mislead an entire field of research,” Dr Schrag told the US National Institutes of Health (NIH).
Science, the publication of AAAS – American Association for the Advancement of Science, conducted its own investigation of the research, finding “strong support for Dr. Schrag’s suspicions”.
Ms Bik told the newspaper: ‘The experimental results obtained might not have been the desired results.
“These data may have been altered to…better fit a hypothesis.”
German psychiatrist Aloiz Alzheimer first identified plaques in the brains of dementia patients in 1906.
A study in the 1980s then suggested that beta-amyloid was to blame for the buildup.
But hundreds of trials over the next 20 years to finally find a therapy that targets the toxic buildup of proteins in the brain have failed.
The theory had lost momentum until the landmark University of Minnesota paper in 2006, which has become the basis for hundreds of studies since.
Reviewing the images used to prove the effect of beta-amyloid on the mice in the study, Dr. Dennis Selkoe, a Harvard University neurologist, said “there are definitely at least 12 or 15 images for which I would agree that there is no other explanation” than manipulation.
Dr Sara Imarisio, head of research at Alzheimer’s Research UK, said: ‘These allegations are extremely serious.
“While we have not seen all of the published findings that have been questioned, any allegations of scientific misconduct should be investigated and addressed as appropriate.”
“Researchers need to be able to trust the findings of their peers, so they can continue to make progress for people affected by conditions like dementia.”
She described the amyloid protein as “at the center of the most influential theory of how Alzheimer’s disease develops in the brain.”
Dr Imarisio said: ‘But the research that has been questioned focuses on a very specific type of amyloid.
“These claims do not compromise the vast majority of knowledge accumulated over decades of research on the role of this protein in disease.”
Nature is investigating the concerns and will provide an editorial response at a later date.
He said: “In the meantime, readers are urged to exercise caution when using the results reported therein.”
The authors of the paper say they “still have faith” that beta-amyloid plaques play a major role in Alzheimer’s disease and stand behind their original findings.
A spokesperson for the University of Minnesota said, “The university will follow its processes to review the issues raised by the claims.
“At this time, we have no further information to provide.”
Dr. Richard Oakley, Associate Director of Research at the Alzheimer Society, told The Times: “We know that many types of amyloid contribute to brain cell death in dementia.
“If what is suggested here ends up being true, we certainly wouldn’t need to throw the baby out with the bathwater.”