Figure 1.

Microtubules in axons and dendrites consist of a stable region towards the minus end of the microtubule and a labile region towards the plus end, as well as a pool of free tubulin subunits. Microtubule severing is a normal event in the neuron, when tightly regulated. Abnormal (deregulated) microtubule severing is posited to account for microtubule loss in AD. Severing in the stable region of the microtubule would create two new microtubules, with fairly minimal disassembly of either one. Severing in the labile region of the microtubule would result in notably more disassembly. Severing at the end of the microtubule would result in disassembly. Because known microtubule-severing proteins favour the stable region of the microtubule, treatment of AD with a microtubule-stabilizing drug may mitigate disassembly that occurs as an aftereffect of the severing, but the severing events themselves would likely increase.