title: Anesthesia and tau pathology.
abstract: Alzheimer's disease (AD) is the most common form of dementia and remains a growing worldwide health problem. As life expectancy continues to increase, the number of AD patients presenting for surgery and anesthesia will steadily rise. The etiology of sporadic AD is thought to be multifactorial, with environmental, biological and genetic factors interacting together to influence AD pathogenesis. Recent reports suggest that general anesthetics may be such a factor and may contribute to the development and exacerbation of this neurodegenerative disorder. Intra-neuronal neurofibrillary tangles (NFT), composed of hyperphosphorylated and aggregated tau protein are one of the main neuropathological hallmarks of AD. Tau pathology is important in AD as it correlates very well with cognitive dysfunction. Lately, several studies have begun to elucidate the mechanisms by which anesthetic exposure might affect the phosphorylation, aggregation and function of this microtubule-associated protein. Here, we specifically review the literature detailing the impact of anesthetic administration on aberrant tau hyperphosphorylation as well as the subsequent development of neurofibrillary pathology and degeneration.
authors.affiliation: Department of Anesthesiology, Columbia University, New York, NY 10032, United States. Electronic address: raw9@columbia.edu.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Whittington
authors.forename: Alexis
authors.initials: A
authors.lastname: Bretteville
authors.forename: Maya F
authors.initials: MF
authors.lastname: Dickler
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Planel
mesh_terms: D000758:Anesthesia / Q000009:adverse effects*; D006801:Humans; D024801:Tauopathies / Q000209:etiology*
keywords: 3-repeat tau isoforms; 3R; 3×Tg-AD; 4-repeat tau isoforms; 4R; AD; AKT/PKB; APP; Alzheimer's disease; Anesthesia; Aβ; BDNF; CSF; CaMKII; Dex; ERK; GABA; GSK-3β; JNK; Kinase; MAC; MAPK; MT; MWM; Morris water maze; N-methyl d-aspartate receptor; NFT; NMDA-R; NR2B; PP1; PP2A; PP2B; PS-1; Phosphatase; Ser; Src; Tau; Tau-SH-SY5Y cells; Thr; amyloid-β; amyloid-β precursor protein; brain-derived neurotrophic factor; c-Jun N-terminal kinase; calcium/calmodulin-dependent protein kinase II; cdk5; cerebrospinal fluid; cyclin-dependent kinase 5; dexmedetomidine; extracellular signal-regulated kinase; glycogen synthase kinase-3β; human neuroblastoma cells constitutively expressing human tau with 3 microtubule-binding domains; i.p.; intra peritoneal; microtubule; minimum alveolar concentration; mitogen-activated protein kinase; neurofibrillary tangles; presenilin-1; protein kinase B; protein phosphatase 1; protein phosphatase 2A; protein phosphatase 2B; serine; short for sarcoma, a non-receptor tyrosine kinase; subunit 2B of NMDA receptor; threonine; triple transgenic Alzheimer's disease mouse model; γ-aminobutyric acid
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