Is blood-brain barrier a probable mediator of non-invasive brain stimulation effects on Alzheimer's disease?

Alzheimer's disease (AD) is a complex neurodegenerative disease with no existing treatment leading to full recovery. The blood-brain barrier (BBB) breakdown usually precedes the advent of first symptoms in AD and accompanies the progression of the disease. At the same time deliberate BBB opening may be beneficial for drug delivery in AD. Non-invasive brain stimulation (NIBS) techniques, primarily transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have shown multiple evidence of being able to alleviate symptoms of AD. Currently, TMS/tDCS mechanisms are mostly investigated in terms of their neuronal effects, while their possible non-neuronal effects, including mitigation of the BBB disruption, are less studied. We argue that studies of TMS/tDCS effects on the BBB in AD are necessary to boost the effectiveness of neuromodulation in AD. Moreover, such studies are important considering the safety issues of TMS/tDCS use in the advanced AD stages when the BBB is usually dramatically deteriorated. Here, we elucidate the evidence of NIBS-induced BBB opening and closing in various models from in vitro to humans, and highlight its importance in AD.