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

作者：Qiang Wang, Xiaomei Zhong, Pengbo Gao, Zhidai Xiao, Ben Chen, Haoye Tan, Qin Liu, Kexin Yao, Shuang Liang, Jingyuan Li, Mingfeng Yang, Danyan Xu, Gaohong Lin, Zhangying Wu, Haishan Shi, Min Zhang, Xiaolei Shi, Huanmin Liu, Yijie Zeng, Yunheng Chen, Yicheng Lin, Shuwei Zhang, Cong Ouyang, Shihan Tian, Y. Gan, Mingyong Zeng, Jieqin Lv, Xiang Liang, Yuwang Cheng, Jianwen Guo, Pengcheng Ran, Yuping Ning, Huarong Zhou · 发表于：Alzheimer s & Dementia · 年份：2025 · DOI：10.1002/alz.70465 · 被引用次数：5 · 研究领域：Folate and B Vitamins Research、Advanced MRI Techniques and Applications、Sulfur Compounds in Biology

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 s...