华中科技大学朱铃强小组近日取得一项新成果。经过不懈努力，他们的最新研究探明了脊髓Tau病理通过CCK神经元失调诱导阿尔茨海默病的触觉缺陷和认知障碍。相关论文于2025年11月18日发表在《自然—神经科学》杂志上。

在这里，该课题组人员发现阿尔茨海默病（AD）患者的触觉功能受损，这种损害与蒙特利尔认知评估得分呈负相关，与Tau病理呈正相关。研究小组在症状前3×Tg AD小鼠中观察到类似的缺陷，并发现脊髓中表达胆囊收缩素（CCK）的神经元极易受到Tau病理的影响。在脊髓表达CCK的神经元中表达突变的Tau-P301S异常激活转录因子c-Maf，抑制CCK神经元并诱导触觉缺陷，而沉默Tau或c-Maf可恢复AD模型小鼠的触觉并改善认知。总之，这些功能获得和功能丧失的研究表明，脊髓CCK神经元中的Tau病理有助于触觉功能障碍和认知功能。以触觉为目标可能是预测阿尔茨海默病患者认知障碍进展的一种有希望的策略。

据了解，体感处理已被证明与大脑发育和认知功能相关，但触觉缺陷是否以及如何影响认知能力下降仍不清楚。

附：英文原文

Title: Spinal cord Tau pathology induces tactile deficits and cognitive impairment in Alzheimer’s disease via dysregulation of CCK neurons

Author: Zhou, Yang, Li, Wen-Lian, Liu, Zhi-Qiang, Ai, Wen-Qing, Kou, Jia-Xin, Fan, Hong-Wei, Han, Zhi-Tao, Hu, Ya-Zhuo, Zhang, Hong-Hong, Jia, Jian-Jun, Zeng, Yan, Guo, Zi-Yuan, Man, Heng-Ye, Lu, You-Ming, Liu, Dan, Zhu, Ling-Qiang

Issue&Volume: 2025-11-18

Abstract: Somatosensory processing has been shown to be correlated with brain development and cognitive function, but whether and how tactile sensory deficits affect cognition decline remains unclear. Here we show that tactile function is impaired in individuals with Alzheimer’s disease (AD), and this impairment is inversely correlated with Montreal Cognitive Assessment scores and positively correlated with Tau pathology. We observed similar deficits in presymptomatic 3×Tg AD mice and find that cholecystokinin (CCK)-expressing neurons in the spinal cord are highly vulnerable to Tau pathology. Expressing mutant Tau-P301S in spinal cord CCK-expressing neurons aberrantly activates the transcription factor c-Maf, inhibits CCK neurons and induces tactile deficits, whereas silencing Tau or c-Maf restores tactile sensation and improves cognition in AD model mice. Together, these gain- and loss-of-function studies demonstrate that Tau pathology in spinal cord CCK neurons contributes to tactile dysfunction and cognitive function. Targeting tactile sensation may be a promising strategy for predicting the progression of cognitive impairment in AD.

DOI: 10.1038/s41593-025-02137-4

Source: https://www.nature.com/articles/s41593-025-02137-4