Piel Johannes Heinrich Alexander, Bargemann Leon, Leypoldt Frank, Wandinger Klaus-Peter, Dargvainiene Justina
Department of Neurology, University Hospital Schleswig-Holstein, Kiel, Germany.
Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein, Kiel, Germany.
Front Neurol. 2024 Mar 19;15:1356575. doi: 10.3389/fneur.2024.1356575. eCollection 2024.
Delirium represents a common terminal pathway of heterogeneous neurological conditions characterized by disturbances in consciousness and attention. Contemporary theories highlight the acute impairment of synaptic function and network connectivity, driven by neuroinflammation, oxidative stress, and neurotransmitter imbalances. However, established biomarkers are still missing. Innovative diagnostic techniques, such as single-molecule array analysis, enable the detection of biomarkers in blood at picomolar concentrations. This approach paves the way for deeper insights into delirium and potentially therapeutic targets for tailored medical treatments. In a retrospective 3-year study, we investigated seven biomarkers indicative of neuroaxonal damage [neurofilament light chain (NFL), ubiquitin carboxyl-terminal hydrolase (UCHL-1), and tau protein], microglial activation [glial fibrillary acidic protein (GFAP) and soluble triggering receptor expressed on myeloid cells 2 (sTREM2)], and synaptic dysfunction [synaptosomal-associated protein 25 (SNAP-25) and neuronal pentraxin 2 (NPTX2)]. The analysis of 71 patients with delirium, Alzheimer's disease (AD), and non-AD controls revealed that serum NFL levels are higher in delirium cases compared to both AD and non-AD. This suggests that elevated NFL levels in delirium are not exclusively the result of dementia-related damage. Serum tau levels were also elevated in delirium cases compared to controls. Conversely, cerebrospinal fluid (CSF) SNAP-25 showed higher levels in AD patients compared to controls only. These findings add to the increasing body of evidence suggesting that serum NFL could be a valuable biomarker of neuroaxonal damage in delirium research. Although SNAP-25 and NPTX2 did not exhibit significant differences in delirium, the exploration of synaptic biomarkers remains promising for enhancing our understanding of this condition.
谵妄是多种神经系统疾病常见的终末途径，其特征为意识和注意力障碍。当代理论强调，神经炎症、氧化应激和神经递质失衡会导致突触功能和网络连接性急性受损。然而，目前仍缺乏成熟的生物标志物。单分子阵列分析等创新诊断技术能够检测皮摩尔浓度血液中的生物标志物。这种方法为深入了解谵妄以及为定制化医疗治疗确定潜在治疗靶点铺平了道路。在一项为期3年的回顾性研究中，我们调查了7种指示神经轴突损伤的生物标志物[神经丝轻链（NFL）、泛素羧基末端水解酶（UCHL-1）和tau蛋白]、小胶质细胞活化标志物[胶质纤维酸性蛋白（GFAP）和髓系细胞表面表达的可溶性触发受体2（sTREM2）]以及突触功能障碍标志物[突触体相关蛋白25（SNAP-25）和神经元五聚体蛋白2（NPTX2）]。对71例谵妄患者、阿尔茨海默病（AD）患者和非AD对照者的分析显示，谵妄患者血清NFL水平高于AD患者和非AD对照者。这表明谵妄患者NFL水平升高并非完全是由痴呆相关损伤所致。与对照组相比，谵妄患者血清tau水平也有所升高。相反，仅AD患者脑脊液（CSF）中的SNAP-25水平高于对照组。这些发现进一步证明，血清NFL可能是谵妄研究中神经轴突损伤的重要生物标志物。尽管SNAP-25和NPTX2在谵妄患者中未表现出显著差异，但探索突触生物标志物对于加深我们对这种疾病的理解仍具有重要意义。
