Premium
P3‐164: Cellular effects of APOE4: Implications for Alzheimer's disease
Author(s) -
Rao Rammohan,
Patent Alexander,
Zhang Qiang,
Flores Sonia,
Bredesen Dale
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.1604
Subject(s) - apolipoprotein e , neurotoxicity , amyloid precursor protein , neurite , allele , alzheimer's disease , proteolysis , cleavage (geology) , biology , chemistry , microbiology and biotechnology , endocrinology , medicine , biochemistry , disease , gene , toxicity , in vitro , enzyme , paleontology , fracture (geology)
concern in Alzheimer’s disease (AD) patients. Interestingly, it has been suggested that the pathological mechanism(s) underlying POCDmimic AD. Indeed, anesthesia might be a risk factor for the development of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Patients with AD are considered to be particularly at risk for some of the cognitive side effects of anesthesia, and there is also concern that general anesthesia is a risk factor for AD, with in vitro and in vivo studies suggesting that anesthetics may promote and intensify the neuropathogenesis of AD. Methods: After a short review of the clinical literature on anesthesia and AD, we will focus on describing the impact of anesthesia on the two pathological hallmarks of AD: beta-amyloid (Abeta) accumulation and aberrant tau phosphorylation and aggregation, with an emphasis on our most recent data. Results: Evidence from in vitro and animal models demonstrate that exposure to inhaled anesthetics, such as isoflurane and halothane, can increase Abeta production, enhance Abeta oligomerization, and promote plaque formation, while exposure to intravenous anesthetics, such as propofol, thiopental or chloral hydrate, has no effect. We have also demonstrated that exposure to isoflurane could lead to tau hyperphosphorylation, detachment from microtubules and enhanced aggregation in vivo, albeit indirectly, by inducing hypothermia in mouse models of tauopathies. On the other hand, some anesthetics such as propofol also have a direct effect on tau phosphorylation, as demonstrated by maintaining the animals normothermic. Conclusions:While there has been clinical interest on the relation between anesthesia and AD for at least a quarter of a century, the biochemical consequences of anesthesia on AD neuropathogenic pathways have only begun to be studied very recently. Overall, epidemiological evidence establishing a link between anesthetic exposure and the risk of AD remains controversial. On the other hand, clinical studies examining AD biomarkers, and studies exploring the impact of anesthetics on Abeta and tau, converge to indicate that anesthetics could affect AD pathogenesis, either directly or indirectly.