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阿尔茨海默病中的癫痫发作

Seizures in Alzheimer's disease.

作者信息

Born H A

机构信息

Department of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

出版信息

Neuroscience. 2015 Feb 12;286:251-63. doi: 10.1016/j.neuroscience.2014.11.051. Epub 2014 Dec 4.

Abstract

Alzheimer's disease (AD) increases the risk for late-onset seizures and neuronal network abnormalities. An elevated co-occurrence of AD and seizures has been established in the more prevalent sporadic form of AD. Recent evidence suggests that nonconvulsive network abnormalities, including seizures and other electroencephalographic abnormalities, may be more commonly found in patients than previously thought. Patients with familial AD are at an even greater risk for seizures, which have been found in patients with mutations in PSEN1, PSEN2, or APP, as well as with APP duplication. This review also provides an overview of seizure and electroencephalography studies in AD mouse models. The amyloid-β (Aβ) peptide has been identified as a possible link between AD and seizures, and while Aβ is known to affect neuronal activity, the full-length amyloid precursor protein (APP) and other APP cleavage products may be important for the development and maintenance of cortical network hyperexcitability. Nonconvulsive epileptiform activity, such as seizures or network abnormalities that are shorter in duration but may occur with higher frequency, may contribute to cognitive impairments characteristic of AD, such as amnestic wandering. Finally, the review discusses recent studies using antiepileptic drugs to rescue cognitive deficits in AD mouse models and human patients. Understanding the mechanistic link between epileptiform activity and AD is a research area of growing interest. Further understanding of the connection between neuronal hyperexcitability and Alzheimer's as well as the potential role of epileptiform activity in the progression of AD will be beneficial for improving treatment strategies.

摘要

阿尔茨海默病(AD)会增加迟发性癫痫发作和神经网络异常的风险。在更为常见的散发性AD中,AD与癫痫发作的共现率有所升高。最近的证据表明,包括癫痫发作和其他脑电图异常在内的非惊厥性网络异常在患者中可能比以前认为的更为常见。家族性AD患者癫痫发作的风险更高,在早老素1(PSEN1)、早老素2(PSEN2)或淀粉样前体蛋白(APP)发生突变以及APP重复的患者中都发现了癫痫发作。本综述还概述了AD小鼠模型中的癫痫发作和脑电图研究。淀粉样β(Aβ)肽已被确定为AD与癫痫发作之间的一个可能联系,虽然已知Aβ会影响神经元活动,但全长淀粉样前体蛋白(APP)和其他APP裂解产物可能对皮质网络过度兴奋的发生和维持很重要。非惊厥性癫痫样活动,如持续时间较短但可能更频繁发生的癫痫发作或网络异常,可能导致AD的认知障碍,如遗忘性徘徊。最后,综述讨论了最近使用抗癫痫药物挽救AD小鼠模型和人类患者认知缺陷的研究。了解癫痫样活动与AD之间的机制联系是一个越来越受关注的研究领域。进一步了解神经元过度兴奋与阿尔茨海默病之间的联系以及癫痫样活动在AD进展中的潜在作用将有助于改进治疗策略。

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