Altered dopamine modulation of LTD-like plasticity in Alzheimer's disease patients

Objective: Mechanisms of synaptic plasticity like long term depression (LTD) are altered in experimental models of Alzheimer's disease (AD). LTD-like plasticity mechanisms has not been yet fully investigated in AD patients. Methods: Here we studied the effects of low frequency (1. Hz) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex in a group of patients with a diagnosis of probable AD, compared to healthy age-matched controls (HS). Moreover, we tested the effects of a single dose of orally administered L-dopa, one of the key neurotransmitters in modulating synaptic plasticity mechanisms, on rTMS induced plasticity. Results: We found that in AD patients the 1. Hz rTMS protocol did not induce the expected inhibitory effect, while a long lasting inhibition of MEP was observed in HS. In addition, L-dopa induced a clear form of reversal of the direction of plasticity in HS that was not evident in AD. Conclusions: Dopamine modulation of LTD-like plasticity is impaired when tested in AD patients. Significance: These findings provide evidence of possible dysfunction of dopaminergic transmission in AD patients.