Perellón-Alfonso Ruben, Abellaneda-Pérez Kilian, Pileckyte Indre, Cabello-Toscano María, Mulet-Pons Lídia, Vaqué-Alcázar Lídia, Cattaneo Gabriele, Redondo-Camós María, España-Irla Goretti, Delgado-Gallen Selma, Sánchez Javier Solana, Zetterberg Henrik, Tormos Jose M, Franzmeier Nicolai, Pascual-Leone Alvaro, Bartrés-Faz David
Department of Medicine, Faculty of Medicine and Health Sciences, and Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Heliyon. 2024 Dec 10;10(24):e41118. doi: 10.1016/j.heliyon.2024.e41118. eCollection 2024 Dec 30.
In early-stage Alzheimer's disease (AD) amyloid-β (Aβ) deposition can induce neuronal hyperactivity, thereby potentially triggering activity-dependent neuronal secretion of phosphorylated tau (p-tau), ensuing tau aggregation and spread. Therefore, cortical excitability is a candidate biomarker for early AD detection. Moreover, lowering neuronal excitability could potentially complement strategies to reduce Aβ and tau buildup. There is, however, a lack of understanding of the relationship between cortical excitability and p-tau increase . Therefore, in a sample of 658 healthy middle-aged (between the ages of 40 and 65) participants of the Barcelona Brain Health Initiative cohort study, we examined the relation of blood-based tau, phosphorylated at amino acid 181 (p-tau181), reflecting neuronal p-tau secretion; neurofilament light chain (NfL), as a passively released control for p-tau181; and electroencephalography (EEG) markers of cortical excitability. A subsample of 47 participants also completed a controlled brain perturbation approach via transcranial magnetic stimulation (TMS) with concurrent EEG. Results show that both spontaneous (i.e., resting-state) and perturbation-based TMS-EEG markers, are associated with blood p-tau181, particularly in older individuals. The perturbation-based marker was a significantly more sensitive predictor of p-tau181 concentration than the spontaneous resting state EEG-based marker. The relationships observed are not present for the NfL control. These results show that relationships between p-tau181 and cortical excitability are present in healthy middle-aged subjects and that p-tau181 increases may reflect activity-dependent secretion.
在早期阿尔茨海默病（AD）中，淀粉样蛋白-β（Aβ）沉积可诱导神经元活动亢进，从而可能触发磷酸化tau蛋白（p-tau）的活性依赖性神经元分泌，继而导致tau蛋白聚集和扩散。因此，皮质兴奋性是早期AD检测的候选生物标志物。此外，降低神经元兴奋性可能补充减少Aβ和tau蛋白积累的策略。然而，目前对皮质兴奋性与p-tau增加之间的关系尚缺乏了解。因此，在巴塞罗那脑健康倡议队列研究的658名健康中年（40至65岁）参与者样本中，我们研究了反映神经元p-tau分泌的血液中181位氨基酸磷酸化的tau蛋白（p-tau181）、作为p-tau181被动释放对照的神经丝轻链（NfL）与皮质兴奋性的脑电图（EEG）标志物之间的关系。47名参与者的子样本还通过经颅磁刺激（TMS）并同步EEG完成了一种可控的脑扰动方法。结果表明，自发（即静息状态）和基于扰动的TMS-EEG标志物均与血液中的p-tau181相关，尤其是在老年人中。与基于自发静息状态EEG的标志物相比，基于扰动的标志物是p-tau181浓度更敏感的预测指标。对于NfL对照，未观察到上述关系。这些结果表明，在健康中年受试者中存在p-tau181与皮质兴奋性之间的关系，且p-tau181增加可能反映了活性依赖性分泌。
