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Researchers Link Alzheimer’s to Lack of Specific Protein
August 15, 2011 — A new clue to understanding one of the causes of Alzheimer's disease was unveiled in an article published Sunday (Aug. 14) in Nature Neuroscience online. Kara Pratt, a new faculty member in the University of Wyoming Neuroscience Center, is the study's lead investigator.
Neurons, the cells of the brain and the nervous system, are amazingly flexible and adaptable, says Pratt, who led the project as a post-doctoral researcher at the University of Washington School of Medicine.
When proteins receive a lot of information from other neurons, they compensate by turning down their synaptic strengths ("input gain"). Conversely, Pratt says, when stimulated at lower than normal frequencies, they turn up their synaptic strengths. This is a form of neural plasticity referred to as homeostasis, which allows neurons to function stably in the midst of extreme changes in activity levels.
She says in people with Alzheimer's disease, it has been hypothesized that brain neurons may lose their flexibility. The most common way in which familial (inherited) Alzheimer' disease is inherited is by a mutation in a protein called presenilin.
The researchers found that neurons that do not have presenilin are not adaptable -- are unable to change their gain -- when activity levels are altered for long periods of time. Pratt says the researchers also tested the compensatory response in neurons from transgenic mice engineered to express a mutated form of presenilin. These neurons also failed to adapt to changing amounts of stimulation.
"Our experiments indicate that presenilin is essential for neurons to remain adaptable," Pratt says. "Lack of this type of adaptability could contribute to brain dysfunction underlying Alzheimer's disease."
Pratt is setting up a laboratory in the UW Department of Zoology and Physiology to study forms of neuron adaptability and other forms of neural plasticity in the developing visual system of the African clawed frog tadpole.
This research was conducted in Jane Sullivan's laboratory in the Department of Physiology and Biophysics at the University of Washington School of Medicine. Other authors on the paper are University of Washington undergraduate student Eric Zimmerman and David. G. Cook, with the Veterans Affairs Medical Center Geriatric Research Education and Clinical Center, Seattle, Wash.
The project was funded by the American Health Assistance Foundation, the National Institutes of Health and the Veteran's Affairs Office of Research and Development Medical Research Service.
University of Wyoming researcher Kara Pratt is the lead author of an article published in Nature Neuroscience online.