MAPT and Alzheimer disease: Importantly, although Aβ is generally localized toward the synapses, evidence from AD and Downs syndrome (DS) with early AD symptoms exhibit intraneuronal Aβ1–42 accumulation that precedes Tau pathology and extracellular Aβ plaque formation (Takahashi et al., 2017; Welikovitch et al., 2018; Capetillo-Zarate et al., 2012), which would support the hypothesis of Aβ1–42 as an intraneuronal infection defense mechanism.