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

ObjectiveMechanisms 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.MethodsHere 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.ResultsWe 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.ConclusionsDopamine modulation of LTD-like plasticity is impaired when tested in AD patients.SignificanceThese findings provide evidence of possible dysfunction of dopaminergic transmission in AD patients.