Electrophysiological and cerebrovascular effects of the alpha-secretase-derived form of amyloid precursor protein in young and middle-aged rats.

ABSTRACT

Cleavage of the beta-amyloid precursor protein (APP) by alpha-secretase releases a secreted form of APP (sAPP) from cells. sAPP is released from neurons in an activity-dependent manner and is believed to play roles in synaptic plasticity and neuroprotection. We determined whether sAPP modulates electrophysiological and cerebrovascular processes in vivo. The effects of recombinant sAPP, applied by intracerebroventricular infusion, on hippocampal and cortical electroencephalographic (EEG) activity and hippocampal blood flow in young adult and middle-aged Long-Evans rats were measured. sAPP increased the power spectrum density of low frequency EEG bands in the hippocampus and cortex of middle-aged rats without affecting hippocampal blood flow. The neurophysiological effects of sAPP were observed in middle-aged, but not in young rats. The results of this study indicate that hippocampal and cortical electrophysiological processes are sensitive to sAPP, whereas the cerebral vasculature may not be regulated by sAPP. The age-dependent change in the sensitivity of neuronal activity to sAPP suggests the possibility of an important role for this APP product in brain functioning in mid life.