Effects of transcranial magnetic stimulation on neurobiological changes in Alzheimer's disease (Review)

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and brain neuronal loss. A pioneering field of research in AD is brain stimulation via electromagnetic fields (EMFs), which may produce clinical benefits. Noninvasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS), have been developed to treat neurological and psychiatric disorders. The purpose of the present review is to identify neurobiological changes, including inflammatory, neurodegenerative, apoptotic, neuroprotective and genetic changes, which are associated with repetitive TMS (rTMS) treatment in patients with AD. Furthermore, it aims to evaluate the effect of TMS treatment in patients with AD and to identify the associated mechanisms. The present review highlights the changes in inflammatory and apoptotic mechanisms, mitochondrial enzymatic activities, and modulation of gene expression (microRNA expression profiles) associated with rTMS or sham procedures. At the molecular level, it has been suggested that EMFs generated by TMS may affect the cell redox status and amyloidogenic processes. TMS may also modulate gene expression by acting on both transcriptional and post‑transcriptional regulatory mechanisms. TMS may increase brain cortical excitability, induce specific potentiation phenomena, and promote synaptic plasticity and recovery of impaired functions; thus, it may re‑establish cognitive performance in patients with AD.

Keywords: Alzheimer's disease; biomarker; brain stimulation; neurobiology; transcranial magnetic stimulation.

Figure 1.

Schematic representation of the proposed paradigm demonstrating neurochemical changes in normal aging and AD, and the effects of TMS on these neurobiological changes, indicating that TMS may restore brain function. Aβ, amyloid-β; AD, Alzheimer's disease; APP, amyloid-β precursor protein; BACE1, β-site APP-cleaving enzyme 1; BDNF, brain-derived neurotrophic factor; CTFs, C-terminal fragments; NAA/Cr, N-acetylaspartate/creatine; NeuN, neuronal nuclear protein; NGFs, nerve growth factors; NMDAR, N-methyl-D-aspartate receptor; rTMS, repetitive transcranial magnetic stimulation; TrkB, tropomyosin receptor kinase B; zif268, Zinc finger-containing transcription factor 268.

Figure 2.

Proposed mechanism of cognitive decline and deterioration of neural plasticity throughout life, which may worsen by mild cognitive impairment and accentuate a maladaptive path to AD. Non-invasive brain stimulation or aerobic exercise improves cognitive ability and increases neural plasticity. Therefore, non-invasive brain stimulation or aerobic exercise exerts a neuroprotective effect on AD. AD, Alzheimer's disease.