all these events could represent a vicious cycle which ultimately favors Ab plaque formations. As matter of fact, somatostatinergic transmitter replacement is a potentially viable strategy in the treatment of AD, even though the pharmacological restoration of this deficit has not been unequivocally associated to a recovery of normal cognitive performances. In this framework, we tested the octreotide effect on IDE expression, a somatostatin analogue currently used in the treatment of acromegaly, pituitary adenomes and pancreatic tumors. Here, we show that, like somatostatin, octreotide increases IDE expression and secretion, although the effects are generally reduced compared to the endogenous modulator. Somatostatin binds all five receptor subtypes with high affinity, whereas octreotide is a selective agonist, binding to receptor subtypes 2 and 5 with high affinity and with moderate affinity to subtype 3. Therefore, this evidence might explain the discrepancy between sst and its analogue concerning the positive modulation of IDE expression, even though additional factors cannot be ruled out. Interestingly, we also observed that in astrocytes, incubation with somatostatin does not have any significant detectable effect of IDE expression, reinforcing the physiological relevance of somatostatin action on IDE secretion in microglia cells. This discrepancy is probably due to the different expression pattern of sst receptor on microglia and astrocytes. In our previous work, we reported that somatostatin is an allosteric modulator of IDE enzymatic activity on a fluorogenic Ab-peptide. Here, we show that somatostatin addition to the culture medium of BV-2 cells rapidly affects the amyloid b-peptide extracellular concentration: after 1 h of stimulation, we observe a negative correlation between Ab concentration and sst concentration. The lack of similar evidence in supernatants from IDE-silenced cells suggests that the decrease in Ab levels is fully attributable to the modulation of IDE activity secreted before sst administration. As a whole, the reported data indicate that somatostatin regulates IDE expression, secretion and catalytic activity in microglia. These results are intriguing, considering that a microglia pharmacological manipulation is thought to play a neuroprotective role at least in the early stages of AD, since these cells cluster around senile plaques promoting Ab phagocytosis and degradation. Therefore, a correlation can be envisaged between the regulation of IDE activity and the microglial immunological function during the development of AD, opening a new therapeutic scenario for the control of AD in the early phases.