Transgenic AD mice overproducing Aβ show hyper-activation as detected by calcium oscillations even prior to amyloid plaques, while tau transgenic mice show hypo-excitation even prior to tangles (Busche et al., 2019), underscoring the pathogenic roles of more soluble forms of both Aβ and tau prior to their neuropathological AD hallmark lesions traditionally viewed as the toxic aggregates. This evidence concerns the gene MAPT and Alzheimer disease.