The kinetics of single-amperometric exocytotic events has been measured in chromaffin cells of C57 mice and in an APP/PS1 mouse model of Alzheimer's disease (AD). K+ depolarisation causes a burst of spikes that indicate the quantal release of the single-vesicle content of catecholamine. The kinetic analysis of 278 spikes from 10 control cells and 520 spikes from 18 APP/PS1 cells shows the following features of the latter compared with the former: (i) 45% lower t(1/2); (ii) 60% smaller quantal size; (iii) 50% lower decay time. Spike feet also showed 60% smaller quantal size. Immunofluorescence and thioflavin staining showed no amyloid beta (A beta) burden in adrenal medulla slices of APP/PSI mice that however exhibited dense A beta plaques in the cortex and hippocampus. Furthermore, acetylcholinesterase staining of adrenal medulla indicated no apparent differences in the innervation by splanchnic cholinergic nerve terminals of chromaffin cells from control and APP/PS1 mice. This is the first report identifying subtle differences in the last steps of exocytosis that could be an indication of synaptic dysfunction of the secretory machinery not linked to A beta burden in AD. (C) 2012 Elsevier Inc. All rights reserved.