139. D2 agonist administration restores impaired LTP-like cortical plasticity in AD patients

Abstract

In a recent study with theta burst stimulation (TBS) we showed that LTP (long-term-depression)-like cortical plasticity is impaired in AD patients. We recently showed that in AD patients the treatment with a subtype-2 receptor dopaminergic agonist (D2) leads to an enhancement of short latency afferent inhibition (SLAI), a neurophysiological measure under cholinergic control. We aimed at investigating whether administration of D2 agonist could modulate cortical plasticity induced with TBS over primary motor cortex (M1) in AD patients. We tested the impact of two weeks administration of D2 agonist (rotigotine) on LTP/LTD-like effects induced respectively by means of intermittent (i-) and continuous (c-) TBS delivered over M1 in eight mild AD patients. After two weeks of D2 agonist administration we observed a marked change in the iTBS protocol effects, revealing that LTP-like plasticity was strikingly enhanced (p > 0.05), while the cTBS protocol did not show similar remarkable modifications. As expected, SLAI was also partially restored by D2 agonist therapy, confirming our recent findings. These results increasingly highlight the role of dopamine in the pathophysiology of AD and suggest that a dysfunction of D2-like receptors is involved in abnormal cortical plasticity in AD. Investigate dopaminergic contribute in AD therapy.