The aim of this study was to explore concentrations differences of soluble amyloid precursor protein (sAPP) α and β in blood plasma in patients with probable Alzheimer's disease (AD) and cognitively healthy age-matched control subjects, as well as patients with behavioural variant frontotemporal dementia (bvFTD). Concentrations of sAPPα and β were measured using enzyme-linked immunosorbent assay technology in 80 patients with probable AD, 37 age-matched control subjects and 14 patients with bvFTD. Concentration differences were explored using parametric tests. Significantly decreased plasma concentrations in the AD group compared with both the control group and the bvFTD group were detected for sAPPβ (P = 0.03 for both group comparisons), but not for sAPPα. The study provides a further piece of evidence in support of sAPPβ as a promising new biomarker of AD, which may potentially improve the diagnostic accuracy of existing markers and also enable a less invasive diagnostic workup. Further research is required to establish normal ranges and to replicate the results in independent cohorts including larger numbers of participants covering a wider spectrum of cognitive impairment.