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. Author manuscript; available in PMC: 2016 Jun 2.
Published in final edited form as: Neuron. 2012 Dec 6;76(5):871–885. doi: 10.1016/j.neuron.2012.11.020

Figure 10. ApoE Sets the Stage and Response to Neuronal Injury Triggers Neuropathology.

Figure 10

(1) Injury to neurons induces the synthesis of apoE. ApoE (apoE4 > apoE3) is susceptible to proteolytic cleavage in neurons, and the neurotoxic fragments that are generated escape the secretory pathway and cause mitochondrial dysfunction and cytoskeletal alterations. This is most likely to occur when apoE4 is expressed (apoE4 > apoE3) due to its abnormal protein conformation (instability and domain interaction). (2) Exogenous apoE, primarily from astrocytes, could cause neuronal injury and could generate neurotoxic fragments by being shunted to the ER/Golgi apparatus, where proteolysis could occur. In addition, exogenous apoE does impact Aβ clearance/deposition. (3) Aβ expression can be induced by injured/stressed neurons, and together with other injurious agents could perpetuate the toxic cycle of injury in neurons. This would include apoE synthesis followed by proteolytic cleavage, toxic fragment formation, and neuropathology.