MAPT and Senile plaques: However, others hold that poorly detectable soluble Aβ42-os are the earliest LOAD drivers (Selkoe, 2008a,b; Crimins et al., 2013; Kayed and Lasagna-Reeves, 2013), bringing about p-Tau-os, NFTs, and synaptic pathology in the total absence of senile plaques (reviewed by Klein, 2013).