title: Human Alzheimer and inflammation biomarkers after anesthesia and surgery.
abstract: BACKGROUND
  The prevalence of postoperative cognitive disturbance, coupled with growing in vitro, cell, and animal evidence suggesting anesthetic effects on neurodegeneration, calls for additional study of the interaction between surgical care and Alzheimer neuropathology. The authors studied human cerebrospinal fluid (CSF) biomarkers during surgery.
  
  
  METHODS
  Eleven patients undergoing idiopathic nasal CSF leak correction were admitted to this Institutional Review Board-approved study. Lumbar subarachnoid catheters were placed before the procedure. Anesthesia was total intravenous propofol or remifentanil or inhalational sevoflurane, depending on provider choice. CSF samples were taken after catheter placement (base), at procedure end (0 h), and then at 6, 24, and 48 h. CSF was analyzed using xMAP Luminex immunoassay (Luminex, Austin, TX).
  
  
  RESULTS
  Of the 11 patients (age range, 53 ± 6 yr), 8 were women; 4 received intravenous anesthesia, 6 sevoflurane, and 1 mixed. Procedures lasted 6.4 ± 2 h. Mean CSF amyloid-β(1-42) remained unchanged, but total-tau and phosphorylated-tau181P increased progressively until at least 48 h. Total-tau, phosphorylated-tau, or amyloid-β(1-42) concentrations were not different between anesthetic groups. CSF interleukin-10, S100Beta, and tumor necrosis factor α were increased similarly in both anesthetic groups at 24 h, but interleukin-6 was increased more in the inhalational group.
  
  
  CONCLUSIONS
  These data indicate a robust neuroinflammatory response, including not only the usual markers (interleukin-6, tumor necrosis factor α, interleukin-10), but also S100Beta and tau, markers of injury. The total-tau/amyloid-β(1-42) ratio increased in a pattern consistent with Alzheimer disease, largely because of an increase in total-tau rather than a decline in amyloid-β(1-42). The differences in CSF interleukin-6 concentrations suggest that anesthetic management may make a difference in neuroinflammatory response.
authors.affiliation: Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Junxia X
authors.initials: JX
authors.lastname: Tang
authors.forename: Dimitry
authors.initials: D
authors.lastname: Baranov
authors.forename: Mary
authors.initials: M
authors.lastname: Hammond
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.forename: Maryellen F
authors.initials: MF
authors.lastname: Eckenhoff
authors.forename: Roderic G
authors.initials: RG
authors.lastname: Eckenhoff
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000758:Anesthesia; D000769:Anesthesia, Inhalation; D000771:Anesthesia, Intravenous; D000906:Antibodies / Q000032:analysis; D015415:Biomarkers / Q000032:analysis* / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007118:Immunoassay; D007249:Inflammation / Q000134:cerebrospinal fluid / Q000378:metabolism*; D016753:Interleukin-10 / Q000134:cerebrospinal fluid; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011184:Postoperative Period; D009418:S100 Proteins / Q000134:cerebrospinal fluid; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D000906:Antibodies; D015415:Biomarkers; D015850:Interleukin-6; D010446:Peptide Fragments; D009418:S100 Proteins; D014409:Tumor Necrosis Factor-alpha; C090308:amyloid beta-protein (40-1); D016875:tau Proteins; D016753:Interleukin-10