FIGURE 8.

Timeline summary of observed events on Aβ-treated hippocampal neurons. The earliest events we observed were activation of caspase and calpain proteases, which display maximal activity within 20 min of Aβ treatment and return to normal levels by 4 h. Erk1/2 and Akt activities are depleted within 30 min to 1 h of Aβ treatment. GSK3β and Cdk5 activation also occurred rapidly and remained elevated throughout the entire time-course. These events precede and overlap with changes in Tau biochemistry, loss of full-length Tau, and accumulation of 17- and 24-kDa Tau fragments. The surprising lack of sustained Tau phosphorylation is depicted as an early spike (phosphorylated epitopes 181, 205, 262, and 400) and subsequent reduction. Events observed that are not depicted in this figure include reduced tubulin immunofluorescence between 8 and 24 h and the rapid and sustained increase in tubulin acetylation after Aβ treatment.