The established biomarkers of Alzheimer's disease (AD) require invasive endeavours or presuppose sophisticated technical equipment. Consequently, new biomarkers are needed. Here, we report that plasma levels of soluble amyloid precursor protein β (sAPPβ), a protein of the initial phase of the amyloid cascade, were significantly lower in patients with symptomatic AD (21 with mild cognitive impairment due to AD and 44 with AD dementia) with AD-typical cerebral hypometabolic pattern compared with 27 cognitively healthy elderly individuals without preclinical AD. These findings yield further evidence for the potential of sAPPβ in plasma as an AD biomarker candidate.