title: Open-heart surgery increases cerebrospinal fluid levels of Alzheimer-associated amyloid β.
abstract: BACKGROUND
  Neurocognitive dysfunction occurs frequently after open-heart surgery. It has been suggested that cognitive decline after cardiac surgery with cardiopulmonary bypass (CPB) could be a functional consequence of Alzheimer's disease (AD)-like neuropathological changes. The aim of the present study was to evaluate the cerebrospinal fluid (CSF) levels of amyloid β peptide (Aβ(1-42) ) and soluble fragments of amyloid precursor protein (sAPP) as well as the cerebral inflammatory response to open-heart surgery.
  
  
  METHODS
  Ten patients undergoing aortic valve replacement with CPB were included. CSF was obtained the day before and 24 h after surgery for assessment of CSF levels of Aβ(1-42)  α-cleaved sAPP and β-cleaved sAPP (sAPP-β). Furthermore, CSF and serum levels of the inflammatory cytokines: tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) were also assessed.
  
  
  RESULTS
  Cardiac surgery with CPB increased CSF levels of Aβ(1-42)  from 447 ± 92 to 641 ± 83 ng/l (P = 0.011), while CSF levels of sAPP-β decreased from 276 ± 35 to 192 ± 21 ng/ml (P = 0.031). CSF levels of TNF-α increased from ≤ 0.60 to 0.79 ± 0.26 ng/l (P = 0.043), IL-6 from 1.89 ± 0.53 to 22.8 ± 6.9 ng/l (P = 0.003) and IL-8 from 39.8 ± 7.8 to 139 ± 18.3 ng/l (P < 0.001).
  
  
  CONCLUSIONS
  Cardiac surgery with CPB causes a profound cerebral inflammatory response, which was accompanied by increased post-operative CSF levels of the AD biomarker Aβ(1-42) . We hypothesize that these changes may be relevant to Alzheimer-associated amyloid build-up in the brain and cognitive dysfunction after cardiac surgery with CPB.
authors.affiliation: Department of Cardiothoracic Anaesthesia and Intensive Care, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. bjorn.reinsfelt@vgregion.se
authors.forename: B
authors.initials: B
authors.lastname: Reinsfelt
authors.forename: A
authors.initials: A
authors.lastname: Westerlind
authors.forename: K
authors.initials: K
authors.lastname: Blennow
authors.forename: H
authors.initials: H
authors.lastname: Zetterberg
authors.forename: S-E
authors.initials: SE
authors.lastname: Ricksten
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D016207:Cytokines / Q000134:cerebrospinal fluid; D004660:Encephalitis / Q000134:cerebrospinal fluid / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016207:Cytokines