Anesthesia Increases Risk of Developing Alzheimer's Disease

A new study has found that anesthesia with isoflurane is safe for normal mice, but potentially harmful for mice with mutations of the amyloid precursor protein (APP), a genetic risk factor for Alzheimer's disease (AD).

Researchers at the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED; Madrid, Spain) and Hospital Ramón y Cajal (Madrid, Spain) examined the long lasting behavioral changes and amyloid pathology of AD in both normal mice (WT) and mice with APP mutations (AbetaPP{swe}), following anesthesia with isoflurane. Repetitive anesthesia was administered twice a week for three months, on mice aged 7 to 10 months of age. The researchers examined the effects of the anesthesia with isoflurane on survival, behavior, apoptosis in hippocampal cells, amyloid-beta (Abeta) peptide and tau patterns, chaperones, and autophagy.

The researchers found that AbetaPP{swe} mice treated with isoflurane had increased mortality, less responsiveness after anesthesia, long lasting reduced exploratory behavior, increased number of apoptotic cells, increased ratio of proapoptotic proteins in the hippocampus, reduced astroglial and increased microglial responses, increased Abeta aggregates and high molecular weight peptides, abnormal chaperone responses, and reduced autophagy. These effects were not present in the WT mice, suggesting that the deleterious impact of isoflurane on behavior, survival, neuronal cell death, and processing of proteins involved in neurodegeneration is restricted only to subjects with increased susceptibility. The study was published in the January 2010 issue of the Journal of Alzheimer's Disease.

"Before surgery requiring anesthesia, it may be ideal to know the genetic background of the patients so that the drugs used and the pattern of anesthesia may be personalized accordingly,” said coauthor Justo García de Yébenes, M.D., of the department of neurobiology at CIBERNED.

Until recently, the most important genetic risk factor known for AD was considered the presence of the allele E4 of the apolipoprotein E, but recently other genetic polymorphisms of risks have been identified. Once these polymorphisms are identified, and their relative impact on the pathogenesis of AD are known, a simple, automatic test for risk of AD could be performed in patients designated for surgery under general anesthesia, and the anesthetic protocol could be modified accordingly.

Related Links:
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas
Hospital Ramón y Cajal