Alzheimer's Disease Research Group, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.
Faculty of Mathematical Sciences, University of Valencia, 46100 Burjassot, Spain.
Int J Mol Sci. 2024 May 13;25(10):5317. doi: 10.3390/ijms25105317.
Alzheimer disease (AD) is a heterogeneous and complex disease in which different pathophysiological mechanisms are involved. This heterogenicity can be reflected in different atrophy patterns or clinical manifestations. Regarding biochemical pathways involved in early AD, lipid metabolism plays an important role; therefore, lipid levels have been evaluated as potential AD diagnosis biomarkers, and their levels could be related to different AD clinical manifestations. Therefore, the aim of this work is to study AD lipid profiles from early AD patients and evaluate their clinical significance. For this purpose, untargeted plasma lipidomic analysis was carried out in early AD patients ( = 31) diagnosed with cerebrospinal fluid (CSF) biomarkers. Cluster analysis was carried out to define early AD subgroups according to the lipid levels. Then, the clinical significance of each lipid profile subgroup was studied, analyzing differences for other variables (cognitive status, CSF biomarkers, medication, comorbidities, age, and gender). The cluster analysis revealed two different groups of AD patients. Cluster 1 showed higher levels of plasma lipids and better cognitive status than Cluster 2. However, no differences were found for the other variables (age, gender, medication, comorbidities, cholesterol, and triglycerides levels) between both groups. Plasma lipid levels could differentiate two early AD subgroups, which showed different cognitive statuses. However, further research with a large cohort and longitudinal study evaluating the clinical evolution of these patients is required. In general, it would involve a relevant advance in the knowledge of AD pathological mechanisms, potential treatments, and precision medicine.
阿尔茨海默病(AD)是一种异质性和复杂的疾病,其中涉及不同的病理生理机制。这种异质性可以反映在不同的萎缩模式或临床表现上。关于涉及早期 AD 的生化途径,脂质代谢起着重要作用;因此,脂质水平被评估为潜在的 AD 诊断生物标志物,其水平可能与不同的 AD 临床表现有关。因此,这项工作的目的是研究早期 AD 患者的 AD 脂质谱,并评估其临床意义。为此,对通过脑脊液(CSF)生物标志物诊断的早期 AD 患者(n = 31)进行了非靶向性血浆脂质组学分析。进行聚类分析以根据脂质水平定义早期 AD 亚组。然后,研究了每个脂质谱亚组的临床意义,分析了其他变量(认知状态、CSF 生物标志物、药物、合并症、年龄和性别)的差异。聚类分析显示 AD 患者有两种不同的亚组。簇 1 显示出较高的血浆脂质水平和较好的认知状态,而簇 2 则相反。然而,两组之间在其他变量(年龄、性别、药物、合并症、胆固醇和甘油三酯水平)方面没有差异。血浆脂质水平可以区分两个具有不同认知状态的早期 AD 亚组。然而,需要进行具有较大队列和纵向研究的进一步研究,以评估这些患者的临床演变。总的来说,这将涉及到 AD 病理机制、潜在治疗方法和精准医学方面的重要进展。