Transgenic Mouse Models, General Anesthetics, and Alzheimer Disease: Findings from Preclinical Studies

Alzheimer's disease (AD) is a neurodegenerative pathology outlined by severe memory impairment and by a developing disruption of cognitive functions. Unfortunately, in contrast with many published data on this disorder, no successful pharmacological approaches and/or therapeutic drugs are available up to now. It has been postulated that the environmental factors (e.g., medications) through the interaction with genetic factors, are able to modulate AD. Growing shreds of evidence highlighted a presumable role of general anesthetics in progression of neurodegenerative processes, including AD. Interestingly, it has been hypothesized an association between anesthetic exposure and postoperative impairment of cognitive trajectory, in terms of postoperative cognitive dysfunction, and AD progression. Specifically, a hypothesis quite overtly postulates that especially inhaled anesthetics may have important effects on the progression of AD, leading to a severe cognitive impairment, although this is still debated. To shed light on this issue, and considering that it is not possible to perform studies in humans, many studies have been performed on AD transgenic animal models featuring neurofibrillary tangles, amyloid beta accumulation (plaque), and behavioral changes due to cognitive dysfunction. In this chapter, we highlight and describe these studies and the methodologies used. Findings emerged from these studies are inconclusive and indicate that anesthetics may promote, or not, the progression of AD, depending on the different experimental conditions, and probably anesthetics are not alone responsible for the cognitive impairment in the investigated animal models. Thus, further research in this paramount field is urgently needed.