APP and early-onset autosomal dominant Alzheimer disease: Amyloid Precursor Protein (APP) is ubiquitously expressed in humans and its proteolytic product amyloid beta (Aβ) can form amyloid plaque, whose accumulation is one of the characteristic pathological features of Alzheimer's Disease (AD).26,27 We and others have previously identified an rG4 at the 3′UTR in APP transcript.28,29 Nevertheless, the structural characterization of APP 3′UTR rG4, especially in the presence of native flanking sequences, is lacking, and the cellular visualization as well as potential mechanism of the inhibitory role of APP 3′UTR rG4 in translation remain elusive.