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LTP (Long-Term-Depression)-like cortical plasticity in Alzheimer disease (AD) patients is impaired. The dopamine involvement in controlling cortical plasticity in AD is still debated. We aimed at investigating whether administration of a D2 agonist could modulate cortical plasticity in AD, as measured by theta burst stimulation (TBS) protocols applied over primary motor cortex. Three groups of mild AD patients were tested before and after four weeks of treatment with rotigotine, rivastigmine or placebo. Each patient was evaluated for plasticity induction of LTP/LTD-like effects using respectively intermittent TBS (iTBS) or continuous TBS (cTBS). Central cholinergic activity was evaluated by means of short latency afferent inhibition (SLAI) protocol. Neuropsychological evaluations were performed to assess cognitive functions. At baseline AD patients showed the previously described pattern of impaired LTP-like cortical plasticity. After four weeks of D2 agonist administration we observed a remarkable change in the LTP-like plasticity. Cholinergic activity was increased by both rotigotine and rivastigmine groups. Neuropsychological testing showed an improvement in the MMSE and in executive functions. Our findings highlight a role for dopamine in AD pathophysiology suggesting that a dysfunction of D2-like receptors is involved in mechanisms of altered cortical plasticity and providing implications for new therapies based on dopaminergic stimulation.

AD patients are characterized by an impairment of Long Term Potentiation (LTP)-like cortical plasticity. AD patients have a weakened Short Latency Afferent Inhibition (SLAI), a neurophysiological measure under cholinergic control. It’s been proposed that high levels of T-tau in AD patients CSF are related to a faster cognitive decline and more malignant form of dementia. Aim of this study is to investigate the relation between CSF values of beta-amyloid, T-tau and P-tau and cortical plasticity in a sample of AD patients. By means of repetitive transcranial magnetic stimulation we tested in 55 AD patients the LTP/LTD-like effects induced by the intermittent TBS (iTBS) and continuous TBS (cTBS) protocols, and the efficacy of SLAI circuits. K-means cluster analysis including the 3 CSF biomarkers was performed.The three resulting clusters differed by the value of T-tau: cluster 1 (low levels); cluster 2 (intermediate levels); cluster 3 (high levels). Cluster 2 showed more impaired LTP-like cortical plasticity and SLAI efficiency, while cluster 1 and cluster 3 have surprisingly the same pathological trends. Our results shed light on the role of tau protein in the physiopathology of AD, showing a similar U shaped-curve related to the level of LTP impairment and SLAI deficiency.