The finding, reported this week in Proceedings of the National Academy of Sciences, provides a novel therapeutic target for development of Alzheimer’s medications, Dr. Oddo said. Alzheimer’s and other dementias currently impair 5.3 million Americans, including more than 340,000 Texans.
In patients with Alzheimer’s disease, accumulation of a protein called amyloid-β (Aβ) blocks memory formation by destroying synapses, the sites where neurons share information. Autopsies of the brains of some Alzheimer’s patients also reveal tangles caused by a protein called tau.
Enhancing CBP does not alter the Aβ or tau physiology but operates on a different recovery mechanism: It restores activity of a protein called CREB and increases levels of another protein called brain-derived neurotrophic factor (BDNF).
“One way by which CBP could work is by setting off a domino effect among proteins that carry signals from the synapse to the nucleus of the neuron,” Dr. Oddo said. “Getting signals to the nucleus is necessary for long-term memory.”
A viral vehicle
The research team engineered a harmless virus to deliver CBP to the hippocampus in the temporal lobe. The hippocampus is the brain’s key structure for learning and memory. At 6 months of age, when the CBP delivery took place, the specially bred mice were at the onset of Alzheimer’s-like deficits. Learning and memory were evaluated in a water maze that required mice to remember the location of an exit platform. The mice treated with CBP were compared to diseased mice that received only placebo and to normal, healthy control mice.
Identical to healthy mice
Efficiency in escaping the maze served as signs of learning and memory. In the Alzheimer’s mouse model, performance of the Alzheimer’s mice treated with enhanced CBP was identical to the healthy mice, whereas the placebo-treated Alzheimer’s mice lagged far behind.
A grant from the U.S. National Institute on Aging supported the study. Co-authors are Antonella Caccamo (first author), Monica Maldonado, Alex Bokov, Smita Majumder and Salvatore Oddo (senior author). All are from the UT Health Science Center San Antonio Department of Physiology except Dr. Bokov, who is in the Department of Epidemiology and Biostatistics. All are Barshop Institute for Longevity and Aging Studies members.
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