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2007 Grant - Xie
Inhalation of Anesthetic Isoflurane and Alzheimer's Disease Neuropathogenesis
Zhongcong Xie, M.D., Ph.D.
Massachusetts General Hospital
2007 Investigator-Initiated Research Grant
Studies in animals have suggested that inhaled anesthetics may increase the number of amyloid plaques, one of the key pathological features of the Alzheimer brain. It is currently unknown whether this effect occurs in humans or whether inhaled anesthetics increase the risk of Alzheimer's disease or its rate of onset.
Several studies, including some performed Zhongcong Xie, M.D., Ph.D., and colleagues, have found evidence that the inhaled anesthetic isoflurane can cause biochemical changes associated with Alzheimer pathology. Such changes include (1) activation of enzymes called caspases, which may contribute to the formation of neurofibrillary tangles, another key pathological feature of Alzheimer's; (2) production of beta-amyloid, the key component of amyloid plaques; and (3) the death of brain cells. These studies have been performed in cultured cells or other isolated model systems. It is not known whether isoflurane causes similar changes in the brains of living organisms.
Dr. Xie and colleagues have proposed to study the effects of isoflurane in the brains of mice that have been genetically altered so that their brains develop a disease that mimics Alzheimer's disease. The researchers will focus on how isoflurane affects the activity of caspases, the production of beta-amyloid and the survival of brain cells. They also propose to perform similar experiments in human brain tissue from patients who received isoflurane during surgery to remove brain tissue affected by epilepsy. These studies should help to clarify whether isoflurane anesthesia increases a person's risk for Alzheimer-like brain plaques.