Temporal profiles of accumulation of amyloid beta/A4 protein precursor in the gerbil after graded ischemic stress.

The neurons that accumulate beta/A4 amyloid protein precursor (APP) after transient cerebral ischemia were characterized by comparing their distribution with those destined to suffer delayed neuronal death or those with induction of 72-kDa heat-shock protein. With immunohistochemistry of APP in gerbil brains, no alterations were detected after ischemia for 2 min and subsequent reperfusion for up to 7 days, whereas after ischemia for 3 min and reperfusion for 48 h, a small number of neurons, intensely immunoreactive for APP, were found to be scattered in the CA1 subfield of the hippocampus and the layer V/VI of the frontoparietal cortex. After reperfusion for 24 h following ischemia for 5 or 15 min, a large number of densely stained neurons appeared in the subiculum, and CA3 subfield of the hippocampus, and layers III and V/VI of the frontoparietal cortex. The majority of these neurons did not undergo delayed neuronal death after reperfusion for 72 h and thereafter. APP and heat-shock protein were upregulated in the same regions, but mostly in distinct neurons. These results indicate that APP accumulates in the neurons marginating the regions destined to die, and the majority of these neurons seem to survive after ischemic insult.