Department of Pharmacology, Brain Science and Engineering Institute, CMRI, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
J Neurol Sci. 2011 Jun 15;305(1-2):28-33. doi: 10.1016/j.jns.2011.03.023. Epub 2011 Apr 3.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by an irreversible cognitive decline and neuronal loss associated with neurofibrillary tangles and senile plaques. Mild cognitive impairment (MCI) is a prodromal stage of AD and is associated with memory loss and a high risk of developing AD. Lipocalin 2 (LCN2) is an acute phase protein. Our previous studies have shown that exposure to inflammatory stimuli resulted in elevated LCN2 levels in brain microglia and astrocytes implicating LCN2 in brain inflammation. Therefore, we hypothesize that there may be a significant change in the plasma LCN2 levels in patients with MCI and AD when compared to healthy control subjects.
Forty-one patients with MCI, 62 patients with AD and 38 healthy elderly control subjects were recruited for this study. They were given a comprehensive battery of neuropsychological tests including a mini-mental status examination (MMSE) and clinical dementia rating (CDR). A variety of clinical information was collected from the semi-structured questionnaire administered. The LCN2 levels were measured using a specific enzyme-linked immunosorbent assay in the plasma, which had been collected early in the morning after overnight fasting.
The LCN2 levels were significantly higher in MCI patients compared to the healthy control subjects and AD patients [control vs. MCI (p=0.005); MCI vs. AD (p=0.009)]. There was a significant negative correlation between the LCN2 levels and CDR scores (r=-0.245, p=0.014), and there was a positive correlation between the LCN2 levels and MMSE scores (r=0.317, p=0.001) among all of the MCI and AD patients.
MCI represents a prodromal stage of AD, and inflammation occurs as one of the earliest pathological events in AD. Thus, increased plasma LCN2 levels during MCI could be helpful in predicting the progression from MCI to AD.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,其特征为认知功能不可逆下降和神经元丧失,伴有神经原纤维缠结和老年斑。轻度认知障碍(MCI)是 AD 的前驱阶段,与记忆丧失和发展为 AD 的高风险相关。脂联素 2(LCN2)是一种急性期蛋白。我们之前的研究表明,暴露于炎症刺激会导致脑小胶质细胞和星形胶质细胞中 LCN2 水平升高,提示 LCN2 参与脑炎症。因此,我们假设与健康对照组相比,MCI 和 AD 患者的血浆 LCN2 水平可能会发生显著变化。
本研究纳入了 41 名 MCI 患者、62 名 AD 患者和 38 名健康老年对照组。他们接受了一系列神经心理学测试,包括简易精神状态检查(MMSE)和临床痴呆评定(CDR)。通过半结构化问卷收集了各种临床信息。使用特定的酶联免疫吸附试验测量了清晨空腹采集的血浆中的 LCN2 水平。
MCI 患者的 LCN2 水平明显高于健康对照组和 AD 患者[对照组与 MCI 组(p=0.005);MCI 与 AD 组(p=0.009)]。LCN2 水平与 CDR 评分呈显著负相关(r=-0.245,p=0.014),在所有 MCI 和 AD 患者中,LCN2 水平与 MMSE 评分呈正相关(r=0.317,p=0.001)。
MCI 代表 AD 的前驱阶段,炎症是 AD 最早的病理事件之一。因此,MCI 期间血浆 LCN2 水平升高可能有助于预测从 MCI 进展为 AD。