Antonioni Annibale, Martorana Alessandro, Santarnecchi Emiliano, Hampel Harald, Koch Giacomo
Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy.
Memory Clinic, Department of Systems Medicine, University of Tor Vergata, Rome, Italy.
Alzheimers Dement. 2025 Jun;21(6):e70337. doi: 10.1002/alz.70337.
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, and neuroinflammation. Preclinical research shows disease-specific neurobiological effects of rTMS in AD. Promising data from AD patients suggest the translatability of animal model results. Preclinical data may guide precision medicine strategies through personalized NIBS.
非侵入性脑刺激(NIBS)技术,如重复经颅磁刺激(rTMS),是治疗阿尔茨海默病(AD)的有前景的候选疗法。我们综述了支持rTMS治疗AD的基本作用机制的证据。rTMS在不同的神经生物学和系统神经生理学水平上发挥着深远的作用。通过作用于受刺激神经网络内不同的突触前和突触后结构,它直接或间接地影响各种细胞和分子成分。在AD中,rTMS影响突触可塑性,在宏观水平上诱导持久的结构变化以及功能和结构连接的广泛重组。重要的是,它调节AD中典型受损的神经递质回路,并通过靶向谷氨酸能和γ-氨基丁酸(GABA)能通路恢复兴奋/抑制平衡。此外,rTMS增加神经营养因子,对抗淀粉样蛋白和tau蛋白的积累,并通过减少小胶质细胞活化和促炎细胞因子释放来减轻神经炎症。因此,不断完善的临床前证据可为未来基于AD患者个性化NIBS的精准医学治疗策略提供指导。要点:非侵入性脑刺激(NIBS)技术,如重复经颅磁刺激(rTMS),是治疗阿尔茨海默病(AD)的有前景的候选疗法。rTMS调节神经可塑性、神经传递和神经炎症。临床前研究显示rTMS在AD中有疾病特异性的神经生物学效应。来自AD患者的有前景的数据表明动物模型结果具有可转化性。临床前数据可能通过个性化NIBS指导精准医学策略。
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