Led by Massachusetts General Hospital (MGH) researchers, the study shows how administration of the gas isoflurane can lead to generation of the toxic amyloid-beta (A-beta) protein in the brains of mice.
"These are the first in vivo results indicating that isoflurane can set off a time-dependent cascade inducing apoptosis (cell death) and enhanced levels of the Alzheimer's-associated proteins BACE and A-beta," says Dr. Zhongcong Xie of the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND) and the MGH Department of Anesthesia and Critical Care.
"This work needs to be confirmed in human studies, but it's looking like isoflurane may not be the best anesthesia to use for patients who already have higher A-beta levels, such as the elderly and Alzheimer's patients," adds the lead and corresponding author of the study, published in the Annals of Neurology.
Several studies have suggested that surgery and general anaesthesia may increase the risk of developing Alzheimer's disease, and it is well known that a small but significant number of surgical patients experience a transient form of dementia in the postoperative period.
A study conducted last year showed that applying isoflurane to cultured neural cells led to the generation of A-beta. The current study was designed to see whether the same would happen in mice.
"This study cannot tell us about the long-term effects of isoflurane administration; that's something we will examine in future investigations," says Xie, who is an assistant professor of Anesthesia at Harvard Medical School (HMS) and director of the Geriatric Anesthesia Research Unit in the MGH Department of Anesthesia and Critical Care.
"Until we can directly assess the impact of isoflurane on biomarkers like A-beta levels in the plasma or cerebrospinal fluid of human patients, we cannot conclusively determine its role in increasing the risk for Alzheimer's or postoperative dementia," adds Rudolph Tanzi, PhD, director of the MGH-MIND Genetics and Aging Research Unit, senior author of the study.