The neurobiological foundation of effective repetitive transcranial magnetic brain stimulation in Alzheimer's disease

作者：Annibale Antonioni, Alessandro Martorana, Emiliano Santarnecchi, Harald Hampel, Giacomo Koch · 发表于：Alzheimer s & Dementia · 年份：2025 · DOI：10.1002/alz.70337 · 被引用次数：23 · 研究领域：Transcranial Magnetic Stimulation Studies、Vagus Nerve Stimulation Research、Neurological disorders and treatments

Noninvasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS), are promising candidate therapeutics for Alzheimer's disease (AD). We review the evidence supporting the fundamental mechanisms of action of rTMS treatments in AD. rTMS exerts profound effects at different neurobiological and systems neurophysiological levels. By engaging distinct pre- and postsynaptic structures within the stimulated neural network, it directly or indirectly influences various cellular and molecular components. In AD, rTMS influences synaptic plasticity, inducing lasting structural changes and broad reorganization of functional and structural connectivity at the macroscale level. Importantly, it modulates neurotransmitter circuits characteristically disrupted in AD and restores the excitation/inhibition balance by targeting glutamatergic and γ-aminobutyric acid (GABA)ergic pathways. Moreover, rTMS increases neurotrophic factors, counteracts amyloid and tau accumulation, and mitigates neuroinflammation by reducing microglial activation and pro-inflammatory cytokines release. Therefore, maturing preclinical evidence could guide future precision medicine therapeutic strategies based on personalized NIBS in AD patients. HIGHLIGHTS: Noninvasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS), are promising candidate therapeutics for Alzheimer's disease (AD). rTMS modulates neuroplasticity, neurotransmission...