The Impact of Anesthesia and Surgery on Tau Pathology: A Pre-Clinical and Clinical Review

Abstract

Aim of Review: Alzheimer's disease (AD) remains the most common form of dementia worldwide and is associated with significant morbidity and mortality. One of the major neuropathological hallmarks of AD and other tauopathies are intraneuronal neurofibrillary tangles composed of aggregates of hyperphosphorylated tau protein. Over the last decade, there is increasing concern that anesthesia and surgery may actually impact the neuropathogenesis of AD, including accelerating tau-related pathology.Method: Here, we reviewed the existing pre-clinical and clinical literature focusing on the impact of anesthesia and surgery on tau-related pathology. We also examined literature suggesting that tau may be associated with post-operative cognitive dysfunction (POCD) and may possess utility as a biomarker for predicting cognitive decline in the postoperative period.Recent findings: There is strong evidence that anesthetics can induce tau phosphorylation directly or indirectly by inducing hypothermia. Certain anesthetics, particularly when accompanied by hypothermia, can induce tau hyperphosphorylation and even pro-aggregant changes in tau, which may be associated with cognitive decline. Similarly, certain surgical procedures can induce profound neuroinflammation and cognitive decline that are associated with changes in tau pathology. Human studies have demonstrated that cerebrospinal fluid (CSF) levels of tau can also dynamically change after surgery and anesthesia. Furthermore, the ratio of CSF tau to amyloid-beta levels or vice versa may be useful in identifying patients at risk for delirium or POCD.Summary: Tau phosphorylation and pathology are dynamically altered by anesthesia and surgery in both pre-clinical and clinical studies. Additional pre-clinical studies in transgenic mice, with relevance to human AD, are needed to fully elucidate the mechanisms as well as the functional and neurobehavioral changes associated with changes in tau pathology. Moreover, clinical studies need to focus on the long-term impact of surgery and anesthesia on tau pathology and any causal relationship to postoperative cognitive decline. Finally, the ratio of CSF tau levels to amyloid-beta levels or vice versa may play a significant role in helping to identify patients who are at risk of cognitive decline after surgery and anesthesia. Citation: Robert A. Whittington, Laszlo Virag, Hilana Lewkowitz-Shpuntoff , Emmanuel Planel. The impact of anesthesia and surgery on tau pathology: a pre-clinical and clinical review. J Anesth Perioper Med 2016; 3: 78-89. doi: 10.24015/JAPM.2016.0011This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.