Increase of SCF plasma concentration during donepezil treatment of patients with early Alzheimer's disease

Abstract

Alzheimer's disease (AD) can be treated with inhibitors of the enzyme acetylcholinesterase (AChE). There is evidence that AChE inhibitors promote neuroprotective effects and neurogenesis in the central nervous system (CNS). However, the mechanisms by which AChE inhibitors mediate these effects are still not well understood. One possible mechanism could be the up-regulation of haematopoietic growth factors (HGFs), also known to promote neuroprotective effects and to stimulate neurogenesis in the CNS. In the present study we investigated the impact of a 15-month treatment with the AChE inhibitor donepezil on blood levels of the HGFs stem cell factor (SCF), stromal cell-derived factor 1 (SDF-1), granulocyte colony- stimulating factor (G-CSF) and vascular endothelial growth factor (VEGF) in 19 patients with AD and 45 age-matched healthy controls. Before treatment with donepezil we found in AD patients significantly decreased SCF plasma concentrations (661.1+/-40.0 pg/ml) compared to healthy controls (997.7+/-33.7 pg/ml, p<0.001) but no significant differences between both groups concerning blood levels of SDF-1, G-CSF and VEGF. After 15 months' treatment SCF plasma levels increased significantly in the AD patients (764.5+/-41.5 pg/ml, p=0.016). In addition, we found a significant positive correlation between SCF plasma levels at baseline and changes of cognitive functions over the 15-month period (r=0.521, p=0.022). For the other HGFs we were unable to show a significant impact of donepezil treatment. Our findings indicate that donepezil treatment of AD patients is associated with an up-regulation of SCF plasma levels, which may contribute to neuroprotection and neurogenesis in the CNS.