Journal Article Ppublish
PubMed: 40673357 DOI: 10.1002/alz.70465
Association and interaction of blood homocysteine and p-tau217 levels with temporal cortical thinning and cognitive impairment in Alzheimer's disease.
Alzheimers Dement 21(7):e70465
Authors: Qiang Wang, Xiaomei Zhong, Pengbo Gao, Zhidai Xiao, Ben Chen, Haoye Tan, Qin Liu, Kexin Yao, Shuang Liang, JiaFu 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, Yujing Gan, Mingyong Zeng, Jieqin Lv, Xiang Liang, Yuwang Cheng, Jianwen Guo, Pengcheng Ran, Yuping Ning, Huarong Zhou
Affiliations
- 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.
- Departments of Nuclear Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China.
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Secondary Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China.
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.
MeSH
Dementia, Blood, Alzheimer Disease, Pathology, Cognitive Dysfunction, Biomarkers, Cognition Disorders, Risk Factors, Amyloid, Cerebral Cortical Thinning, Homocysteine