Fig. 7

Schematic representation showing the proposed pathway that mediates dendritic simplification. The formation of Aβ and NMDAR activity are required for dendritic simplification since blocking of Aβ production or inhibition of NMDAR activity abolish the pathology. NMDAR activation leads to pathologic dephosphorylation of dendritic tau, which shows at physiological conditions a higher phosphorylation state. Dephoshorylation increases tau’s activity to stabilize dendritic microtubules, an activity that is mimicked by the microtubule-stabilizing drug EpoD or phosphoblocking tau (Ala htau). Continuous lines show direct effects, and dashed lines show indirect effects with potential intermediate steps