Ultrastructural localization of amyloid protein precursor in the normal and postischemic gerbil brain

Intracellular localization of amyloid protein precursor (APP) in the normal and postischemic gerbil brain was examined by immunoelectron microscopy. In the normal brain, APP immunoreactivity was localized to the multivesicular body, the nuclear membrane, Golgi apparatus and rough endoplasmic reticulum. After ischemia for 5 min and reperfusion for 24 h, some neurons became intensely immunoreactive for APP in the subiculum and CA3 region of the hippocampus and layers III and V/VI of the cerebral cortex. No intense labeling occurred in glial cells. Intensely labeled neurons were characterized by eccentric nuclei and accumulation of cellular organelles in the center of the neuronal perikarya, as well as a strongly immunoreactive nuclear membrane and cisternal structures, which were presumed to be dispersed Golgi apparatus and/or fragmented rough ER. APP immunoreactivity in the multivesicular body suggests re-internalization of APP and its degradation in the endosomal-lysosomal pathway. The ultrastructural features of neurons with intense APP immunoreactivity suggested mild neuronal damage, similar to those found in central chromatolysis. This indicates that accumulation of APP in these neurons is caused by disturbance of axonal transport, although the information does not allow us to exclude the possibility of an increase in APP production.