DOI: 10.1097/01.NT.0000462537.39153.3e
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Issn Print: 1533-7006
Publication Date: 2015/03/05
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Excerpt
Overexpressing a protein that is linked to longevity and cognitive function can prevent memory loss and behavioral effects in transgenic animals destined to develop Alzheimer's disease, according to a new study.
Animals with the human amyloid precursor protein (APP) mutation were crossed with transgenic animals that overexpress a protein called klotho. The animals lived longer and never developed the spatial learning and memory deficits that are expected in the APP transgenic mouse model. Surprisingly, the cognitively fit animals had amyloid plaques and other pathological signs of the disease.
The new study, conducted by scientists at the Gladstone Institutes and the University of California, San Francisco (UCSF), and published in the Feb. 11 issue of the Journal of Neuroscience, offers hope that the klotho gene and its protein may eventually lead to novel therapies for Alzheimer's.
The investigators at UCSF, led by Dena Dubal, MD, PhD, an assistant professor of neurology and the David A. Coulter chair in aging and neurodegenerative disease, have been studying klotho's ability to enhance cognition for several years. Last May, her group, along with colleagues at the Gladstone Institutes, published a study in Cell Reports showing that people who carry a common variant of klotho called KL-VS seem to perform better on a number of cognitive tests.
One in five people are born with the KL-VS variant, Dr. Dubal explained. They produce higher levels of klotho and appear to live 7 to 10 percent longer than those without a KL-VS copy. People with the variant undergo age-related declines in memory and learning but they appear to start at a higher baseline. Their cognitive functions are slightly better throughout life. “Their normal is just better,” said Dr. Dubal. (That is not the case for the small percentage of people who are born with two copies of KL-VS. They appear to have a shorter lifespan and decreased cognitive scores. Dr. Dubal said that they do not know why.
