治疗阿尔茨海默病的电磁场刺激疗法。

Neurology (Chicago, Ill.) Pub Date : 2024-01-01 Epub Date: 2024-01-05
Felipe P Perez, Jorge Morisaki, Haitham Kanakri, Maher Rizkalla
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引用次数: 0

摘要

阿尔茨海默病(AD)是全球最常见的神经退行性痴呆症。阿尔茨海默病是一种多因素疾病,由有毒的β-淀粉样蛋白(Aβ)引起记忆力和功能逐渐衰退,β-淀粉样蛋白是阿尔茨海默病病理变化的关键因素。2022 年,有 650 万美国人患有注意力缺失症,使国家损失 3210 亿美元。治疗注意力缺失症的标准疗法包括乙酰胆碱酯酶抑制剂(AchEIs)、NMDA 受体拮抗剂和单克隆抗体(mAbs)。然而,这些方法要么1)无法有效改善认知能力;2)无法改变疾病进展;3)治疗靶点数量有限;4)容易引起严重的副作用(使用 mAb 会出现脑肿胀、微出血,使用 AchEIs 会出现心动过缓和晕厥);5)无法有效穿过血脑屏障;6)缺乏对疾病衰老过程的了解。目前已有 mAbs 可用于降低 Aβ,但要降低脑内有毒 Aβ 蛋白的水平而又不引发与 mAbs 相关的脑肿胀或微小出血非常困难,这使得 mAbs 的风险效益特征并不明确。一种新型的多靶点、有效且安全的非侵入性方法利用重复电磁场刺激(REMFS)降低了人类神经元和记忆区域中的Aβ水平,防止了神经元死亡,阻止了疾病进展,并改善了AD小鼠的记忆,同时不会引起脑水肿或出血。由于目前的电磁场设备穿透深度差,脑内电磁场分布不均匀,因此这种 REMFS 治疗方法尚未开发用于人类。在这里,我们讨论了这些效应在神经元中的生物学作用,以及设计最佳设备来治疗注意力缺失症的问题。
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Electromagnetic Field Stimulation Therapy for Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative dementia worldwide. AD is a multifactorial disease that causes a progressive decline in memory and function precipitated by toxic beta-amyloid (Aβ) proteins, a key player in AD pathology. In 2022, 6.5 million Americans lived with AD, costing the nation $321billion. The standard of care for AD treatment includes acetylcholinesterase inhibitors (AchEIs), NMDA receptor antagonists, and monoclonal antibodies (mAbs). However, these methods are either: 1) ineffective in improving cognition, 2) unable to change disease progression, 3) limited in the number of therapeutic targets, 4) prone to cause severe side effects (brain swelling, microhemorrhages with mAb, and bradycardia and syncope with AchEIs), 5) unable to effectively cross the blood-brain barrier, and 6) lack of understanding of the aging process on the disease. mAbs are available to lower Aβ, but the difficulties of reducing the levels of the toxic Aβ proteins in the brain without triggering brain swelling or microhemorrhages associated with mAbs make the risk-benefit profile of mAbs unclear. A novel multitarget, effective, and safe non-invasive approach utilizing Repeated Electromagnetic Field Stimulation (REMFS) lowers Aβ levels in human neurons and memory areas, prevents neuronal death, stops disease progression, and improves memory without causing brain edema or bleeds in AD mice. This REMFS treatment has not been developed for humans because current EMF devices have poor penetration depth and inhomogeneous E-field distribution in the brain. Here, we discussed the biology of these effects in neurons and the design of optimal devices to treat AD.

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Electromagnetic Field Stimulation Therapy for Alzheimer's Disease. Epigenetics of Neurotrauma.
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