Transcranial magnetic stimulation: Emerging biomarkers and novel therapeutics in Alzheimer's disease

Alzheimer's disease (AD) is one of the most devastating conditions affecting elderly in Western World. Unfortunately, there are no effective treatments, and patients diagnosed with AD face an uncertain future, caused by the current inability to predict the course of the disease. This is mainly due to the poor comprehension of AD pathophysiology and of patients' clinical heterogeneity. In recent years, several evidences supported the concept that loss of synaptic density could be an early event and precede neuronal degeneration, suggesting that the impairment of synaptic transmission should play a key role in the pathogenesis of different forms of dementia, including AD, frontotemporal dementia and Lewy body dementia. Despite this emerging background it has not been possible to quantify synaptic functioning (or dysfunction) directly in vivo in AD patients. Transcranial magnetic stimulation (TMS) has been recently introduced as a novel approach able to identify the early signatures of synaptic dysfunction characterizing the different forms of AD. We review the novel emerging neurophysiological signatures of AD and how this information may be used as biomarkers for differential diagnosis, disease progression and response to therapy. Finally, we also consider novel therapeutic approaches based on the clinical use of repetitive TMS.