Anesthesia is found to induce hyperphosphorylation of tau at sites related to Alzheimer's disease

10 March 2009

Staten Island, NY—Scientists from The New York State Office of Mental Retardation and Develop-mental Disabilities’ (OMRDD) New York State Institute for Basic Research in Developmental Disabilities (IBR) report today in the March issue of the Journal of Alzheimer’s Disease that anesthesia induces phosphorylation of tau. Tau is a key neuronal protein involved in neurodegeneration in Alzheimer’s disease (AD) and several other neurodegenerative disorders. Anesthesia has previously been found to be associated with cognitive impairment and the risk for AD. This study helps elucidate the molecular mechanisms underlying these associations.

The researchers found that in test animals, anesthesia for short periods (30 seconds to 5 minutes) induced tau phosphorylation at some selective phosphorylation sites to a small but significant extent. Anesthesia for a longer time (1 hour) induced much more dramatic phosphorylation at the same sites, possibly as a result of anesthesia-induced hypothermia. The observation that anesthesia did not induce global hyperphosphorylation of brain proteins, but instead specific hyperphosphorylation of tau protein at the AD-related abnormal hyperphosphorylation sites suggests that tau hyperphosphorylation might be the mechanism that links anesthesia and the risk of cognitive impairment and/or AD.

AD is the most common cause of dementia in adults and affects approximately 27 million individuals worldwide and over four million in the United States alone. Most AD cases are sporadic and are believed to be caused by multiple factors. Understanding the mechanism by which anesthesia may increase the risk for cognitive impairment will help in the design of strategies for preventing and treating dementia and AD. “This is a very important finding related to Alzheimer’s disease,” said OMRDD Commissioner Diana Jones Ritter. “I am pleased that these findings will lead to helping people live richer lives through the research findings.”

The study was carried out by the Brain Metabolism Laboratory at IBR. Headed by Dr. Cheng-Xin Gong, the laboratory is focusing its research on the roles of several signaling and metabolic factors in neurodegeneration and deregulated neurodevelopment, especially related to AD and autism.

These findings were published in the Journal of Alzheimer’s Disease 2009; 16:3 (Run X, Liang Z, Zhang L, Iqbal K, Grundke-Iqbal I, Gong C-X: Anesthesia induces phosphorylation of tau. JAD 16:3; 619-626).

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Co-authors are Xiaoqin Run and Zhihou Liang, of IBR and Huazhong University of Science and Technology, Wuhan, Hubei, China; Lan Zhang, of Xuan-Wu Hospital of the Capital Medical University, Beijing, China; and Khalid Iqbal, Inge Grundke-Iqbal, and Cheng-Xin Gong, of IBR.

This work was supported by the New York State Office of Mental Retardation and Developmental Disabilities, and by grants from the National Institutes of Health, the U.S. Alzheimer’s Association, and the National Natural Science Foundation of China.

Maureen Marlow
Institute for Basic Research in Developmental Disabilities