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.