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A possible mechanistic link between stress and the development of Alzheimer tangles

La Jolla, CA -- Subjecting mice to repeated emotional stress, the kind we experience in everyday life, may contribute to the accumulation of neurofibrillary tangles, one of the hallmarks of Alzheimers disease, report researchers at the Salk Institute for Biological Studies. While aging is still the greatest risk factor for Alzheimers disease, a number of studies have pointed to stress as a contributing factor.

A long-term study of about 800 members of religious orders had found that the people who were most prone to stress were twice as likely to develop Alzheimers disease, but the nature of the link between the two has been elusive, says Paul E. Sawchenko, Ph.D., a professor in the Neuronal Structure and Function Laboratory, who led a phalanx of Salk researchers contributing to the current study.

The groups findings, detailed in this weeks Journal of Neuroscience, suggest that the brain-damaging effects of negative emotions are relayed through the two known corticotropin-releasing factor receptors, CRFR1 and CRFR2, which are part of a central switchboard that mediates the bodys responses to stress and stress-related disorders.

Alzheimers disease is defined by the accumulation of amyloid plaques and neurofibrillary tangles. While plaques accumulate outside of brain cells, tangles litter the inside of neurons. They consist of a modified form of the tau protein, whichin its unmodified formhelps to stabilize the intracellular network of microtubules. In Alzheimer's disease, as well as various other neurodegenerative conditions, phosphate groups are attached to tau. As a result, tau looses its grip on the microtubules, and starts to collapse into insoluble protein fibers, which ultimately cause cell death.

Previous studies had shown that extreme physiological stress, such as plunging mice into ice water or starving them for three days, can induce tau phosphorylation. But what we wanted to know was whether exposure to milder
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Contact: Gina Kirchweger
kirchweger@salk.edu
858-453-4100 x1340
Salk Institute
14-Jun-2007


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