Impaired LTP- but not LTD-Like Cortical Plasticity in Alzheimer's Disease Patients

In animal models of Alzheimer's disease (AD), amyloid-beta fragments interfere with mechanisms of cortical plasticity such as long-term potentiation (LTP) and long-term depression (LTD). In the current study, we applied repetitive transcranial magnetic stimulation over the primary motor cortex (M1) in AD patients and in age-matched healthy controls, using protocols of theta burst stimulation (TBS) that are known to induce plastic changes resembling the LTP and LTD mechanisms described in animal models. AD patients showed consistent LTD-like effects that were comparable to those obtained in healthy controls when submitted to 40 seconds of continuous TBS. Conversely, AD patients did not show any LTP-like after effect when submitted to two different TBS protocols that induced an LTP-like effect in healthy controls such as intermittent TBS and 20 seconds of continuous TBS followed by one minute of muscular contraction. These results demonstrate the impairment of LTP-like together with normal LTD-like cortical plasticity in AD patients.