Yale researchers are one step closer to reversing the effects of Alzheimer’s disease.
Led by Paul Lombroso, professor of neurobiology and psychiatry , an interdepartmental team at the School of Medicine has discovered that removing a certain protein from Alzheimer’s-affected mice can reverse cognitive deficits associated with the disease. The results of the study, published in the Proceedings of the National Academy of Sciences on Oct. 18, provide opportunities for new treatments to be developed for both Alzheimer’s and similar diseases, like schizophrenia and fragile X syndrome, though researchers cautioned that it would take between ten and fifteen years for such a drug to make it onto the commercial marketplace, due to restrictions on human testing.
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“Though there are drugs on the market to treat Alzheimer’s disease they can only mildly slow the progression,” said Christopher Pittenger ’94 GRD ’94, an assistant professor of psychiatry at the School of Medicine and a co-author of the study.
When the researchers crossed a mouse affected by Alzheimer’s with a “knock-out” mouse which lacked the striatal-enriched tyrosine phosphatase protein, they found that the six-month-old “knock-out” mice, though still afflicted with Alzheimer’s disease, performed as well as normal mice on various cognitive tasks. The tasks included locating a transparent platform in a tub of water.
The protein, in a healthy body, serves to help cycle the glutamate receptors on the synapses of neurons, which is a process crucial to learning, Lombroso said. But in patients with Alzheimer’s disease, the protein increases in number until it impedes this process, he explained.
“Normally mice [affected by Alzheimer’s], when they get to be six months of age have difficulty in completing cognitive tasks,” he explained. “But in [the knock-out] mice the results were indistinguishable from a [normal] mouse.”
More significantly, Christopher van Dyck ’78, director of the Alzheimer’s Disease Research Unit at the School of Medicine, said, the study did not address the amyloid hypothesis, a contested theory which places the cause of Alzheimer’s disease with a certain peptide, or series of amino acids.
The peptide in question is considered by some scientists to be toxic, causing increased levels of the studied protein and playing a role in the cognitive degeneration of Alzheimer’s disease, Lombroso said.
The fact that the “knock-out” mice had these toxic peptides makes the results of the study even more interesting, van Dyck said, because the results are not tied to the outcome of the amyloid debate.
“There has been a lot of controversy in the past few weeks and months about the amyloid hypothesis,” said van Dyck, who is also a professor of psychiatry and neurobiology.
But Pittenger said that the study still does not get to the crux of the matter.
“It has a limitation in that it doesn’t target what causes the progression of the disease,” he said.
The study does, however, address how to alleviate the symptoms of Alzheimer’s disease, which Pittenger said offers future opportunities for the development of a drug to treat the condition.
The Lombroso lab has developed a drug which can reduce the protein concentration in mice and reverse the effects of Alzheimer’s on the brain, Pittenger said, though delays in drug approval mean that it will not be available for up to 15 years.
The research, which was done in collaboration with Paul Greengard, the Vincent Astor professor at Rockefeller University and a 2000 Nobel Laureate, was funded by the American Health Assistance Foundation and the National Institutes of Health.