Precision Neuroscience & Neuromodulation Program, Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Siena Brain Investigation & Neuromodulation Lab (Si-BIN Lab), Unit of Neurology and Clinical Neurophysiology, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Precision Neuroscience & Neuromodulation Program, Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Ageing Res Rev. 2024 Nov;101:102509. doi: 10.1016/j.arr.2024.102509. Epub 2024 Sep 19.
Parvalbumin-positive (PV+) basket neurons are fast-spiking, non-adapting inhibitory interneurons whose oscillatory activity is essential for regulating cortical excitation/inhibition balance. Their dysfunction results in cortical hyperexcitability and gamma rhythm disruption, which have recently gained substantial traction as contributing factors as well as potential therapeutic targets for the treatment of Alzheimer's Disease (AD). Recent evidence indicates that PV+ cells are also impaired in Frontotemporal Dementia (FTD) and Dementia with Lewy bodies (DLB). However, no attempt has been made to integrate these findings into a coherent pathophysiological framework addressing the contribution of PV+ interneuron dysfunction to the generation of cortical hyperexcitability and gamma rhythm disruption in FTD and DLB. To fill this gap, we epitomized the most recent evidence on PV+ interneuron impairment in AD, FTD, and DLB, focusing on its contribution to the generation of cortical hyperexcitability and gamma oscillatory disruption and their interplay with misfolded protein accumulation, neuronal death, and clinical symptoms' onset. Our work deepens the current understanding concerning the role of PV+ interneuron dysfunction across neurodegenerative dementias, highlighting commonalities and differences among AD, FTD, and DLB, thus paving the way for identifying novel biomarkers and potential therapeutic targets for the treatment of these diseases.
钙结合蛋白阳性（PV+）篮状细胞是快速放电、非适应型抑制性中间神经元，其振荡活动对于调节皮层兴奋/抑制平衡至关重要。它们的功能障碍导致皮层过度兴奋和伽马节律紊乱，最近作为阿尔茨海默病（AD）的致病因素和潜在治疗靶点得到了广泛关注。最近的证据表明，PV+细胞在额颞叶痴呆（FTD）和路易体痴呆（DLB）中也受到损害。然而，尚未有人试图将这些发现整合到一个连贯的病理生理学框架中，以解决 PV+中间神经元功能障碍对 FTD 和 DLB 中皮层过度兴奋和伽马节律紊乱的产生的贡献。为了填补这一空白，我们总结了最近关于 AD、FTD 和 DLB 中 PV+中间神经元损伤的证据，重点关注其对皮层过度兴奋和伽马振荡紊乱的产生的贡献，以及与错误折叠蛋白积累、神经元死亡和临床症状发作的相互作用。我们的工作加深了对 PV+中间神经元功能障碍在神经退行性痴呆中的作用的理解，突出了 AD、FTD 和 DLB 之间的共性和差异，为识别这些疾病的治疗的新生物标志物和潜在治疗靶点铺平了道路。
