Nasab Azam Sajjadi, Noorani Fatemeh, Paeizi Zahra, Khani Leila, Banaei Saba, Sadeghi Mohammad, Shafeghat Melika, Shafie Mahan, Mayeli Mahsa, Initiative Adni The Alzheimer's Disease Neuroimaging
NeuroTRACT Association, Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Int J Alzheimers Dis. 2023 Mar 9;2023:3540020. doi: 10.1155/2023/3540020. eCollection 2023.
While cerebrospinal fluid (CSF) core biomarkers have been considered diagnostic biomarkers for a long time, special attention has been recently dedicated to lipoproteins and metabolites that could be potentially associated with Alzheimer's disease (AD) neurodegeneration. Herein, we aimed to investigate the relationship between the levels of CSF core biomarkers including A-42, TAU, and P-TAU and plasma lipoproteins and metabolites of patients with AD from the baseline cohort of the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.
Using the ADNI database, fourteen subclasses of lipoproteins as well as a number of lipids and fatty acids and low-molecular metabolites including amino acids, ketone bodies, and glycolysis-related metabolites in blood samples were measured as potential noninvasive markers, and their association with the CSF core biomarkers was statistically investigated controlling for age and gender.
A total number of 251 AD subjects were included, among whom 71 subjects were negative for the 4 allele and 150 were positive. There was no significant difference between the two groups regarding cognitive assessments, CSF core biomarkers, and lipoproteins and metabolites except the level of A-42 ( < 0.001) and phenylalanine ( = 0.049), which were higher in the negative group. CSF TAU and P-TAU were significantly correlated with medium and small HDL in the negative group, and with extremely large VLDL in the positive group. Our results also indicated significant correlations of metabolites including unsaturated fatty acids, glycerol, and leucine with CSF core biomarkers.
Based on our findings, a number of lipoproteins and metabolites were associated with CSF core biomarkers of AD. These correlations showed some differences in 4 positive and negative groups, which reminds the role of gene status in the pathophysiology of AD development. However, further research is warranted to explore the exact association of lipoproteins and other metabolites with AD core biomarkers and pathology.
虽然脑脊液（CSF）核心生物标志物长期以来一直被视为诊断生物标志物，但最近人们特别关注可能与阿尔茨海默病（AD）神经退行性变相关的脂蛋白和代谢物。在此，我们旨在研究阿尔茨海默病神经影像倡议（ADNI）数据库基线队列中AD患者脑脊液核心生物标志物（包括A-42、TAU和P-TAU）水平与血浆脂蛋白和代谢物之间的关系。
使用ADNI数据库，测量血液样本中14种脂蛋白亚类以及多种脂质、脂肪酸和低分子代谢物（包括氨基酸、酮体和糖酵解相关代谢物）作为潜在的非侵入性标志物，并在控制年龄和性别的情况下对它们与脑脊液核心生物标志物的关联进行统计学研究。
共纳入251名AD受试者，其中71名受试者4等位基因呈阴性，150名呈阳性。两组在认知评估、脑脊液核心生物标志物、脂蛋白和代谢物方面无显著差异，但A-42水平（<0.001）和苯丙氨酸水平（=0.049）除外，阴性组的这两项水平较高。脑脊液TAU和P-TAU在阴性组中与中、小高密度脂蛋白显著相关，在阳性组中与极大极低密度脂蛋白显著相关。我们的结果还表明，包括不饱和脂肪酸、甘油和亮氨酸在内的代谢物与脑脊液核心生物标志物存在显著相关性。
基于我们的研究结果，一些脂蛋白和代谢物与AD的脑脊液核心生物标志物相关。这些相关性在4等位基因阳性和阴性组中显示出一些差异，这提示了基因状态在AD发展病理生理学中的作用。然而，需要进一步研究来探索脂蛋白和其他代谢物与AD核心生物标志物及病理学的确切关联。
