Effects of anesthetic isoflurane and desflurane on human cerebrospinal fluid Aβ and τ level

Anesthesiology. 2013 Jul;119(1):52-60. doi: 10.1097/ALN.0b013e31828ce55d.

Abstract

Background: Accumulation of β-amyloid protein (Aβ) and tau protein is the main feature of Alzheimer disease neuropathogenesis. Anesthetic isoflurane, but not desflurane, may increase Aβ levels in vitro and in animals. Therefore, we set out to determine the effects of isoflurane and desflurane on cerebrospinal fluid (CSF) levels of Aβ and tau in humans.

Methods: The participants were assigned into spinal anesthesia (N=35), spinal plus desflurane anesthesia (N=33), or spinal plus isoflurane anesthesia (N=38) group by randomization using computer-generated lists. Pre- and postoperative human CSF samples were obtained through an inserted spinal catheter. The levels of Aβ (Aβ40 and Aβ42) and total tau in the CSF were determined.

Results: Here, we show that isoflurane, but not desflurane, was associated with an increase in human CSF Aβ40 levels (from 10.90 to 12.41 ng/ml) 24 h after the surgery under anesthesia compared to spinal anesthesia (from 11.59 to 11.08 ng/ml), P=0.022. Desflurane, but not isoflurane, was associated with a decrease in Aβ42 levels 2 h after the surgery under anesthesia (from 0.39 to 0.35 ng/ml) compared to spinal anesthesia (from 0.43 to 0.44 ng/ml), P=0.006. Isoflurane and desflurane did not significantly affect the tau levels in human CSF.

Conclusions: These studies have established a system to study the effects of anesthetics on human biomarkers associated with Alzheimer disease and cognitive dysfunction. These findings have suggested that isoflurane and desflurane may have different effects on human CSF Aβ levels.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdomen / surgery
  • Aged
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Anesthesia, Inhalation*
  • Anesthetics, Inhalation / pharmacology*
  • Blood Loss, Surgical / statistics & numerical data
  • Desflurane
  • Female
  • Humans
  • Isoflurane / analogs & derivatives*
  • Isoflurane / pharmacology*
  • Male
  • Middle Aged
  • Orthopedic Procedures
  • Peptide Fragments / cerebrospinal fluid
  • Socioeconomic Factors
  • Surgical Procedures, Operative
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Peptides
  • Anesthetics, Inhalation
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Desflurane
  • Isoflurane