阿尔茨海默病中血同型半胱氨酸和p-tau217水平与颞叶皮质变薄及认知障碍的关联和相互作用。

Association and interaction of blood homocysteine and p-tau217 levels with temporal cortical thinning and cognitive impairment in Alzheimer's disease.

作者信息

Wang Qiang, Zhong Xiaomei, Gao Pengbo, Xiao Zhidai, Chen Ben, Tan Haoye, Liu Qin, Yao Kexin, Liang Shuang, Li JiaFu, Yang Mingfeng, Xu Danyan, Lin Gaohong, Wu Zhangying, Shi Haishan, Zhang Min, Shi Xiaolei, Liu Huanmin, Zeng Yijie, Chen Yunheng, Lin Yicheng, Zhang Shuwei, Ouyang Cong, Tian Shihan, Gan Yujing, Zeng Mingyong, Lv Jieqin, Liang Xiang, Cheng Yuwang, Guo Jianwen, Ran Pengcheng, Ning Yuping, Zhou Huarong

机构信息

The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China.

Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, Guangdong Province, China.

出版信息

Alzheimers Dement. 2025 Jul;21(7):e70465. doi: 10.1002/alz.70465.

DOI:10.1002/alz.70465

PMID:40673357

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12268315/

Abstract

INTRODUCTION

The relationships between blood homocysteine (Hcy), amyloid beta (Aβ), tau pathology, and their combined effects on cortical thinning and cognitive impairment in Alzheimer's disease (AD) remain poorly understood.

METHODS

Participants were stratified into Aβ+ and Aβ- groups by positron emission tomography. Blood levels of Hcy, AD biomarkers (phosphorylated tau-217 [p-tau217], p-tau181, and Aβ), cortical thickness (via magnetic resonance imaging), and cognitive performance were assessed.

RESULTS

Aβ+ individuals exhibited increased blood Hcy and p-tau217 levels, which negatively correlated with temporal cortical thickness and cognitive function. A significant interaction between Hcy and p-tau217 was observed in Aβ+ participants, with high Hcy exacerbating the detrimental effects of p-tau217 on temporal cortical thinning and cognitive deficits. In Aβ- individuals, Hcy levels were independently associated with tau pathology.

DISCUSSION

Increased Hcy and p-tau217 levels synergistically contribute to cortical thinning and cognitive impairment, highlighting that Hcy may be a modifiable risk factor for AD progression. Highlights Increased blood levels of homocysteine (Hcy) and phosphorylated tau-217 (p-tau217) are independently and interactively associated with temporal cortical thinning and cognitive deficits. Hcy may predominantly affect tau pathology compared to amyloid aggregation, with its impact on neurodegeneration depending on coexisting pathologies. Hcy may serve as a supplementary indicator rather than as an independent predictor in Alzheimer's disease. Hcy may serve as a modifiable risk factor, whereas p-tau217 as a superior diagnostic biomarker and potential therapeutic target.

摘要

引言

血液同型半胱氨酸（Hcy）、β-淀粉样蛋白（Aβ）、tau病理之间的关系，以及它们对阿尔茨海默病（AD）皮质变薄和认知障碍的综合影响仍知之甚少。

方法

通过正电子发射断层扫描将参与者分为Aβ阳性和Aβ阴性组。评估血液中Hcy、AD生物标志物（磷酸化tau-217 [p-tau217]、p-tau181和Aβ）水平、皮质厚度（通过磁共振成像）和认知表现。

结果

Aβ阳性个体的血液Hcy和p-tau217水平升高，这与颞叶皮质厚度和认知功能呈负相关。在Aβ阳性参与者中观察到Hcy和p-tau217之间存在显著相互作用，高Hcy会加剧p-tau217对颞叶皮质变薄和认知缺陷的有害影响。在Aβ阴性个体中，Hcy水平与tau病理独立相关。

讨论

Hcy和p-tau217水平升高协同导致皮质变薄和认知障碍，这突出表明Hcy可能是AD进展的一个可改变的风险因素。要点血液中同型半胱氨酸（Hcy）和磷酸化tau-217（p-tau217）水平升高与颞叶皮质变薄和认知缺陷独立且相互关联。与淀粉样蛋白聚集相比，Hcy可能主要影响tau病理，其对神经退行性变的影响取决于共存的病理情况。在阿尔茨海默病中，Hcy可能作为一个补充指标而非独立预测因子。Hcy可能是一个可改变的风险因素，而p-tau217是一个更好的诊断生物标志物和潜在治疗靶点。