Several lines of evidence suggest that AβPP gene expression could influence risk for Alzheimer's disease (AD). Using a highly sensitive multiplex fluorescent RT-PCR assay, we compared peripheral blood cells expression of AβPP mRNA among sporadic AD patients (n = 133), autosomal dominant early-onset AD cases (ADEOAD, n = 21), Down syndrome patients (n = 21), AD patients with AβPP duplication (n = 9), patients with recent ischemic stroke (n = 25), and healthy controls (n = 58). Compared to healthy controls (median = 0.98), AβPP expression was not increased in sporadic AD patients (median = 1.01, p = 0.42) nor in ADEOAD patients (median = 0.96, p = 0.26). Down syndrome patients as well as patients with AβPP duplication had significantly increased levels of AβPP mRNA compared to controls (median = 1.48 and median = 1.36, p < 0.0001 and p = 0.0007, respectively). A weaker but significant increase in relative amount of AβPP transcripts in patients who suffered from recent stroke was observed (median = 1.14, p = 0.0007). Our results do not support a pathogenic role of AβPP overexpression in sporadic AD although a small subset of patients displays AβPP overexpression in the same range as Down syndrome patients.