Department of Psychiatry and Neurochemistry,Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
J Alzheimers Dis. 2021;79(2):729-741. doi: 10.3233/JAD-201039.
Brevican and neurocan are central nervous system-specific extracellular matrix proteoglycans. They are degraded by extracellular enzymes, such as metalloproteinases. However, their degradation profile is largely unexplored in cerebrospinal fluid (CSF).
The study aim was to quantify proteolytic peptides derived from brevican and neurocan in human CSF of patients with Alzheimer's disease (AD) and vascular dementia (VaD) compared with controls.
The first cohort consisted of 75 individuals including 25 patients with AD, 7 with mild cognitive impairment (MCI) diagnosed with AD upon follow-up, 10 patients with VaD or MCI diagnosed with VaD upon follow-up, and 33 healthy controls and cognitively stable MCI patients. In the second cohort, 31 individuals were included (5 AD patients, 14 VaD patients and 12 healthy controls). Twenty proteolytic peptides derived from brevican (n = 9) and neurocan (n = 11) were quantified using high-resolution parallel reaction monitoring mass spectrometry.
In the first cohort, the majority of CSF concentrations of brevican and neurocan peptides were significantly decreased inVaDas compared withADpatients (AUC = 0.83.0.93, p≤0.05) and as compared with the control group (AUC = 0.79.0.87, p ≤ 0.05). In the second cohort, CSF concentrations of two brevican peptides (B87, B156) were significantly decreased in VaD compared with AD (AUC = 0.86.0.91, p ≤ 0.05) and to controls (AUC = 0.80.0.82, p ≤ 0.05), while other brevican and neurocan peptides showed a clear trend to be decreased in VaD compared with AD (AUC = 0.64.80, p > 0.05). No peptides differed between AD and controls.
Brevican and neurocan peptides are potential diagnostic biomarkers for VaD, with ability to separate VaD from AD.
短蛋白聚糖和神经蛋白聚糖是中枢神经系统特异性细胞外基质蛋白聚糖。它们可被细胞外酶如金属蛋白酶降解。然而，它们在脑脊液（CSF）中的降解谱在很大程度上尚未得到探索。
本研究旨在定量分析阿尔茨海默病（AD）和血管性痴呆（VaD）患者与对照组的人 CSF 中源自短蛋白聚糖和神经蛋白聚糖的蛋白水解肽。
第一队列包括 75 名个体，其中包括 25 名 AD 患者、7 名轻度认知障碍（MCI）患者，随访时诊断为 AD、10 名 VaD 或 MCI 患者，随访时诊断为 VaD，以及 33 名健康对照者和认知稳定的 MCI 患者。在第二队列中，纳入了 31 名个体（5 名 AD 患者、14 名 VaD 患者和 12 名健康对照者）。使用高分辨率平行反应监测质谱法定量分析 20 种源自短蛋白聚糖（n=9）和神经蛋白聚糖（n=11）的蛋白水解肽。
在第一队列中，与 AD 患者相比，VaD 患者的大多数 CSF 短蛋白聚糖和神经蛋白聚糖肽浓度显著降低（AUC=0.83.0.93，p≤0.05），与对照组相比也显著降低（AUC=0.79.0.87，p≤0.05）。在第二队列中，与 AD 相比，VaD 患者的两种短蛋白聚糖肽（B87、B156）的 CSF 浓度显著降低（AUC=0.86.0.91，p≤0.05），与对照组相比也显著降低（AUC=0.80.0.82，p≤0.05），而其他短蛋白聚糖和神经蛋白聚糖肽在 VaD 中也表现出明显的降低趋势与 AD 相比（AUC=0.64.80，p>0.05）。AD 患者与对照组之间无肽差异。
短蛋白聚糖和神经蛋白聚糖肽可能是 VaD 的潜在诊断生物标志物，具有将 VaD 与 AD 区分开来的能力。
