Fig. 9.

AβOs cause pathological tau redistribution. AβOs (ADDLs) induce missorting of Tau and neurofilaments into the somatodendritic compartment of primary hippocampal neurons that suggests a mechanism for AD nerve cell death. Left, top There is no colocalization of Tau and MAP2 in vehicle-treated control cells. Tau is predominantly localized to the axonal compartment (antibody K9JA—green), while MAP2 is localized to the somatodendritic compartment (antibody AP20—red). Left, bottom In ADDL-treated cells (5 μM for 3 h), Tau is redistributed into soma and dendrites (green), where it colocalizes with MAP2 (red). Arrows indicate colocalization of MAP2 and Tau. Adapted from Zempel et al. [191]. Right Data suggest a mechanism for AD neuronal cell death that involves AβO-induced breakdown of Tau sorting and neuronal polarity. Aβ induces missorting of Tau, which in turn leads to a loss of microtubules, impaired trafficking (e.g., of mitochondria), and loss of spines, ultimately leading to neuronal death. Adapted from Zempel and Mandelkow [190]