Serum Cholinesterase Activities Distinguish between Stroke Patients and Controls and Predict 12-Month Mortality

Abstract

To date there is no diagnostic biomarker for mild stroke, although elevation of inflammatory biomarkers has been reported at early stages. Previous studies implicated acetylcholinesterase (AChE) involvement in stroke, and circulating AChE activity reflects inflammatory response, since acetylcholine suppresses inflammation. Therefore, carriers of polymorphisms that modify cholinergic activity should be particularly susceptible to inflammatory damage. Our study sought diagnostic values of AChE and Cholinergic Status (CS, the total capacity for acetylcholine hydrolysis) in suspected stroke patients. For this purpose, serum cholinesterase activities, butyrylcholinesterase-K genotype and inflammatory biomarkers were determined in 264 ischemic stroke patients and matched controls during the acute phase. AChE activities were lower (P < 0.001), and butyrylcholinesterase activities were higher in patients than in controls (P = 0.004). When normalized to sampling time from stroke occurrence, both cholinergic parameters were correlated with multiple inflammatory biomarkers, including fibrinogen, interleukin-6 and C-reactive protein (r = 0.713, r = 0.607; r = 0.421, r = 0.341; r = 0.276, r = 0.255; respectively; all P values < 0.001). Furthermore, very low AChE activities predicted subsequent nonsurvival (P = 0.036). Also, carriers of the unstable butyrylcholinesterase-K variant were more abundant among patients than controls, and showed reduced activity (P < 0.001). Importantly, a cholinergic score combining the two cholinesterase activities discriminated between 94.3% matched pairs of patients and controls, compared with only 75% for inflammatory measures. Our findings present the power of circulation cholinesterase measurements as useful early diagnostic tools for the occurrence of stroke. Importantly, these were considerably more distinctive than the inflammatory biomarkers, albeit closely associated with them, which may open new venues for stroke diagnosis and treatment.

Neuroendocrine hormones as prognostic biomarkers in the setting of acute stroke: overcoming the major hurdles

“…Acetylcholine esterase (AChE) activity has been found higher in cerebrospinal fluid of acute stroke patients compared with healthy controls [66]. Recently, lower serum AChE activities have been found in acute stroke patients compared with controls, and those patients who died after a 12-month follow-up period were found to have lower AChE activities than survivors in the same study [67]. Whether the role of AChE as a marker of the PSNS activity could predict specific post-stroke complications is under investigation.…”

Fluoxetine induces vasodilatation of cerebral arterioles by co‐modulating NO/muscarinic signalling

“…Assays were performed in 0.1 M phosphate buffer, pH 7.4, 0.5 mM dithio-bis-nitrobenzoic acid and 1 mM acetylthiocholine substrate at room temperature [19]. Optical density at 405 nm was monitored for 20 min.…”

Serum Cholinesterase Levels Are Associated With 2-Year Ischemic Outcomes After Angioplasty and Stenting for Peripheral Artery Disease

“…In their study, low CHE was a significant predictor of mortality and thus included in a multivariable risk score that demonstrated an excellent discriminatory power for 10-year survival. Ben Assayag et al 13 reported lower CHE activity in 264 patients with an ischemic stroke compared to healthy controls and found very low CHE activity to be a predictor of mortality in their patient population. The above-described findings together with our observations suggest that cholinergic imbalance affects long-term prognosis in healthy individuals as well as in patients with manifest cardiovascular disease.…”