血清色氨酸、酪氨酸与阿尔茨海默病之间的关系

The Associations of Serum Tryptophan and Tyrosine With Alzheimer’s Disease

目的越来越多的研究表明,代谢物的失衡与阿尔茨海默病(Alzheimer’s disease,AD)之间存在密切的联系。近年来,代谢组学的发展使研究AD周围代谢的特征性变化成为可能。有研究表明,血清色氨酸(tryptophan,Trp)、酪氨酸(tyrosine,Tyr)水平与轻度认知功能障碍(mild cognitive impairment,MCI)、AD相关。本文拟进一步阐明MCI和AD中色氨酸、酪氨酸水平的特征。方法将来自阿尔茨海默病神经影像学倡议1(Alzheimer’s Disease Neuroimaging Initiative-1,ADNI-1)队列的765位参与者,分为认知正常(cognitive normal,CN,n=207)、稳定性轻度认知功能障碍(stable mild cognitive impairments,sMCI,n=201)、进行性认知功能障碍(progressive mild cognitive impairments,pMCI,n=171)和AD所致痴呆(n=186)。分析血清色氨酸、酪氨酸对MCI、AD是否具有诊断价值。分析在不同诊断组中,血清色氨酸、酪氨酸分别与脑脊液生物标志物、脑结构、脑代谢及认知功能之间的关系。结果与CN组相比,sMCI、pMCI、AD组血清色氨酸水平偏低。pMCI组、AD组血清酪氨酸水平显著低于CN组。血清色氨酸对pMCI、AD有诊断价值。血清酪氨酸仅对AD有诊断价值。结论血清色氨酸、酪氨酸有助于AD的早期诊断。色氨酸、酪氨酸的检测可以为AD的病理学机制研究提供新思路。血清色氨酸、酪氨酸与AD核心标志物、认知功能、脑结构、脑代谢之间均无明显相关性,故血清色氨酸、酪氨酸可能不是AD较好的外周生物标志物。

Objective A growing body of research suggests a strong link between metabolic imbalance and Alzheimer’s disease(AD).In recent years,the development of metabolomics makes it possible to study the characteristic changes of peripheral metabolism in AD.Serum levels of tryptophan and tyrosine were associated with mild cognitive impairment(MCI)and AD.The purpose of this study is to further characterize tryptophan and tyrosine levels in MCI and AD.Methods We stratified 765 participants from the Alzheimer’s Disease Neuroimaging Initiative-1(ADNI-1)cohort into cognitively normal(CN;n=207),stable mild cognitive impairment(sMCI;n=201),progressive mild cognitive impairment(pMCI;n=171),and dementia due to AD(n=186).Serum tryptophan and tyrosine were analyzed for diagnostic value of MCI and AD.To evaluate the relationships between serum tryptophan and tyrosine and cerebrospinal fluid(CSF)biomarkers,brain structure(magnetic resonance imaging,MRI),cerebral glucose metabolism(18F-fluorodeoxyglucose-positron emission tomography,FDG-PET),and cognitive declines,through different cognitive subgroups.Results Serum tryptophan was decreased in patients with AD,pMCI or sMCI compared with CN.Serum tyrosine was decreased in patients with AD or pMCI compared with CN.Serum tryptophan has diagnostic value for pMCI and AD.Serum tyrosine has diagnostic value for AD.Conclusion Serum tryptophan and tyrosine contribute to the early diagnosis of AD.The detection of tryptophan and tyrosine can contribute to the pathogenesis of AD.Serum tryptophan and tyrosine were not significantly associated with core AD markers,cognitive function,brain structure and brain metabolism,so serum tryptophan and tyrosine may not be good peripheral AD biomarkers.