February 22, 2016
In the past few years, despite the best efforts of scientists and medical researchers, drug after drug designed to slow or stop the progression of Alzheimer's disease has failed in clinical trials. Some had no effect on the progression of the disease, others made patients' symptoms worse and yet others produced results so equivocal it was difficult to interpret them.
Given this ongoing challenge, some scientists have begun to question the model of the disease many of the drugs assume. Known as the amyloid cascade hypothesis, it posits that the cognitive decline in Alzheimer's is caused by the accumulation in the brain of plaques, or aggregates, of thousands of copies of a peptide called amyloid beta.
Instead of being neurotoxic, the plaques may actually be protective, said Liviu Mirica, associate professor of chemistry in Arts & Sciences at Washington University in St. Louis.
Recent work suggests small aggregates of amyloid-beta peptide, called soluble oligomers, rather than the insoluble plaques may be the neurotoxic form of amyloid beta. This might explain why the disease process seems to start 10-15 years before the plaques become prominent in the brain, he said.
Mirica, who specializes in the design of chemical agents that contain metal ions, called metal complexes, has a clever idea he hopes might help the scores of scientists and research physicians who are struggling to unravel the mechanism of this disease.