Circuitry and Synaptic Dysfunction in Alzheimer’s Disease: A New Tau Hypothesis

Figure 3

pTau protein at MD (microtubule domain) prevents NMDAr overexcitation, which accounts for protection rather than damage. (a) Aβ42 oligomers repeatedly affect neurons by blocking glutamate reuptake (1), which leads to hyperactivation (2), kinase activation (3), Tau hyperphosphorylation, and Tau translocation from the axon to the dendritic spines (4) causing LTP blockade and progressive spine loss (5). (b) Alternatively, Aβ42 oligomers block glutamate reuptake (1), which leads to hyperactivation (2), kinase activation (3), and Tau phosphorylation at MD sites (4), which alternatively promote LTD, preventing further NMDAr-mediated overexcitation and producing neuroprotection (5).