Lam Jordan, Lee Justin, Liu Charles Y, Lozano Andres M, Lee Darrin J
USC Neurorestoration Center, Keck School of Medicine of USC, Los Angeles, CA, 90033, USA.
Department of Neurological Surgery, Keck School of Medicine of USC, Los Angeles, CA, 90033, USA.
Neuromodulation. 2021 Feb;24(2):171-186. doi: 10.1111/ner.13305. Epub 2020 Dec 30.
Treatments for Alzheimer's disease are urgently needed given its enormous human and economic costs and disappointing results of clinical trials targeting the primary amyloid and tau pathology. On the other hand, deep brain stimulation (DBS) has demonstrated success in other neurological and psychiatric disorders leading to great interest in DBS as a treatment for Alzheimer's disease.
We review the literature on 1) circuit dysfunction in Alzheimer's disease and 2) DBS for Alzheimer's disease. Human and animal studies are reviewed individually.
There is accumulating evidence of neural circuit dysfunction at the structural, functional, electrophysiological, and neurotransmitter level. Recent evidence from humans and animals indicate that DBS has the potential to restore circuit dysfunction in Alzheimer's disease, similarly to other movement and psychiatric disorders, and may even slow or reverse the underlying disease pathophysiology.
DBS is an intriguing potential treatment for Alzheimer's disease, targeting circuit dysfunction as a novel therapeutic target. However, further exploration of the basic disease pathology and underlying mechanisms of DBS is necessary to better understand how circuit dysfunction can be restored. Additionally, robust clinical data in the form of ongoing phase III clinical trials are needed to validate the efficacy of DBS as a viable treatment.
鉴于阿尔茨海默病带来的巨大人力和经济成本,以及针对主要淀粉样蛋白和tau蛋白病变的临床试验结果令人失望,治疗阿尔茨海默病的方法亟待开发。另一方面,深部脑刺激(DBS)已在其他神经和精神疾病中取得成功,这引发了人们对将DBS用于治疗阿尔茨海默病的极大兴趣。
我们回顾了关于1)阿尔茨海默病中的神经回路功能障碍和2)用于阿尔茨海默病的DBS的文献。对人体和动物研究分别进行了综述。
在结构、功能、电生理和神经递质水平上,越来越多的证据表明存在神经回路功能障碍。来自人体和动物的最新证据表明,与其他运动和精神疾病类似,DBS有可能恢复阿尔茨海默病中的回路功能障碍,甚至可能减缓或逆转潜在的疾病病理生理过程。
DBS作为一种针对回路功能障碍的新型治疗靶点,是一种治疗阿尔茨海默病的潜在有趣疗法。然而,有必要进一步探索基本疾病病理和DBS的潜在机制,以更好地理解如何恢复回路功能障碍。此外,需要正在进行的III期临床试验形式的有力临床数据来验证DBS作为一种可行治疗方法的疗效。