Acetylcholine synthesis in human CSF: implications for study of central cholinergic metabolism

Investigation of neurological diseases involving central cholinergic dysfunction has led to numerous studies seeking a peripheral marker of cholinergic activity in brain. The main objective of these studies was to determine whether the ACh synthesizing activity present in human CSF was due to the presence of the enzyme choline acetyltransferase (ChAT; 68 kDa). When CSF was fractioned into low and high molecular weight (Mr) components, 80% of the ACh synthesizing activity (ACh-SA) was found to be associated with the fraction less than 10 kDa. The remaining 20% was evenly distributed among fractions in the 5-30, 30-50, 50-300, and 300 kDa fractions. Although boiling destroyed all activity greater than 10 kDa, the ChAT inhibitor NVP, at concentrations equal to or greater than that required to inhibit ChAT in human cortical tissue, did not alter the ACh-SA in either fraction. Results indicate that normal human CSF does not contain ChAT and all ACh-SA in CSF reflects non-enzymatic imidazole/histidine-like catalyzed synthesis.