"We wanted to repeat the study to see if we could build on it, and we couldn't," said David Borchelt, a professor of neuroscience at the University of Florida, noting that "it was important to publish the fact."
"Maybe there should be some caution going forward in regard to patients," he added.
The high profile 2012 study in the US journal Science found that mice treated with bexarotene became rapidly smarter and the plaque in their brains that was causing Alzheimer's started to disappear within hours.
The drug was believed to work by boosting levels of a protein, Apolipoprotein E (ApoE), that helps clear amyloid plaque buildup in the brain, a key hallmark of Alzheimer's disease.
"We were shocked and amazed," lead author Gary Landreth, a professor in the Department of Neurosciences at Case Western Reserve University School of Medicine in Ohio, told AFP when the study was published in February 2012.
"Things like this had never, ever been seen before," he said.
But a key part of science is being able to replicate the findings of any research, and international researchers reported in four separate papers in Science's May 24 edition that they had failed to do so.
Other researchers who published their attempts were Bart De Strooper, director of the VIB Center for the Biology of Disease in Belgium, and Sangram Sisodia, director of the Center for Molecular Neurobiology at the University of Chicago.
The scientists said their studies showed no effect on the plaque levels in three different populations of lab mice treated with bexarotene.
A fourth group of researchers said they observed mental gains in the mice but could not confirm they were achieved by the mechanism initially reported, said co-author Iliya Lefterov, associate professor at the University of Pittsburgh Graduate School of Public Health.
"While we were able to verify that the mice quickly regained their lost cognitive skills and confirmed the decrease in amyloid beta peptides in the interstitial fluid that surrounds brain cells, we did not find any evidence that the drug cleared the plaques from their brains."
The findings should also serve as a warning for doctors not to prescribe bexarotene as an off-label treatment for Alzheimer's, researchers said.
The drug, also known as Targretin, was approved by the US Food and Drug Administration in 1999 for treating a type of skin cancer known as refractory cutaneous T-cell lymphoma.
"Anecdotally, we have all heard that physicians are treating their Alzheimer's patients with bexarotene, a cancer drug with severe side effects," said Robert Vassar, professor of cell and molecular biology at Northwestern University Feinberg School of Medicine.
"This practice should be ended immediately, given the failure of three independent research groups to replicate the plaque-lowering effects of bexarotene."