Lin William Z, Yu Di, Xiong Lisa Y, Zebarth Julia, Wang Ruoding, Fischer Corinne E, Rajji Tarek K, Tang-Wai David F, Tartaglia Carmela, Saposnik Gustavo, Swartz Richard H, Grimes David A, Lang Anthony E, Hegele Robert A, Farhan Sali, Ramirez Joel, Symons Sean, Goubran Maged, Binns Malcolm A, Lou Wendy, Dixon Roger A, Orange Joseph B, Roberts Angela C, Troyer Angela K, Zetterberg Henrik, Herrmann Nathan, Rabin Jennifer S, MacIntosh Bradley J, Masellis Mario, Lanctôt Krista L, Black Sandra E, Swardfager Walter
Department of Pharmacology & Toxicology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Alzheimers Dement. 2025 Jan;21(1):e14376. doi: 10.1002/alz.14376. Epub 2024 Nov 19.
Elevated plasma homocysteine (Hcy) is associated with an increased risk of developing neurodegenerative diseases; however, its relationship with the apolipoprotein E (APOE) ε4 allele has not been well characterized.
Participants clinically diagnosed with Alzheimer's disease or mild cognitive impairment (AD/MCI), frontotemporal dementia, Parkinson's disease, or cerebrovascular disease were stratified by the presence of the APOE ε4 allele. Volumetric magnetic resonance imaging, plasma amyloid/tau/neurodegeneration biomarkers, and cognitive performance were quantified.
Across all diagnostic groups, Hcy was associated with lower brain parenchymal fraction and greater neurofilament light chain in APOE ε4 non-carriers only. In AD/MCI, Hcy was associated with phosphorylated tau 217 in APOE ε4 non-carriers, but not in carriers. Exploratory analyses revealed interactions between Hcy and APOE ε4 on memory and visuospatial function.
Hcy may contribute to neurodegeneration depending on the presence of the APOE ε4 allele and specific disease processes. Trials on vitamin B12 supplementation may consider stratifying by APOE genotype. Highlights Homocysteine (Hcy) was associated with neurodegenerative biomarkers across disease groups. Relationships with Hcy were predominantly found in apolipoprotein E (APOE) ε4 non-carriers. In Alzheimer's disease, associations between Hcy and phosphorylated tau 217 were found in APOE ε4 non-carriers only. Significant interactions existed between Hcy and APOE ε4 status on cognition.
血浆同型半胱氨酸（Hcy）水平升高与神经退行性疾病的发病风险增加相关；然而，其与载脂蛋白E（APOE）ε4等位基因的关系尚未得到充分阐明。
对临床诊断为阿尔茨海默病或轻度认知障碍（AD/MCI）、额颞叶痴呆、帕金森病或脑血管疾病的参与者，根据是否存在APOE ε4等位基因进行分层。对容积磁共振成像、血浆淀粉样蛋白/ tau /神经退行性生物标志物以及认知表现进行量化。
在所有诊断组中，仅在APOE ε4非携带者中，Hcy与较低的脑实质分数和较高的神经丝轻链相关。在AD/MCI中，Hcy与APOE ε4非携带者中的磷酸化tau 217相关，但在携带者中不相关。探索性分析揭示了Hcy与APOE ε4在记忆和视觉空间功能上的相互作用。
Hcy可能根据APOE ε4等位基因的存在和特定疾病过程而导致神经退行性变。维生素B12补充试验可能考虑按APOE基因型进行分层。要点同型半胱氨酸（Hcy）与各疾病组的神经退行性生物标志物相关。与Hcy的关系主要在载脂蛋白E（APOE）ε4非携带者中发现。在阿尔茨海默病中，仅在APOE ε4非携带者中发现Hcy与磷酸化tau 217之间存在关联。Hcy与APOE ε4状态在认知方面存在显著相互作用。
