Open-heart surgery increases cerebrospinal fluid levels of Alzheimer-associated amyloid β.

Abstract

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. 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. 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). 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.