Centro E. Grossi Paoletti, Dipartimento Di Scienze Farmacologiche E Biomolecolari, Università Degli Studi Di Milano, Milano, Italy.
Neurology Unit, IRCCS "San Gerardo Dei Tintori", Monza, and University of Milano-Bicocca, Milano, Italy.
Alzheimers Res Ther. 2023 May 20;15(1):95. doi: 10.1186/s13195-023-01241-6.
The purpose of this study was to evaluate cholesterol esterification and HDL subclasses in plasma and cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients.
The study enrolled 70 AD patients and 74 cognitively normal controls comparable for age and sex. Lipoprotein profile, cholesterol esterification, and cholesterol efflux capacity (CEC) were evaluated in plasma and CSF.
AD patients have normal plasma lipids but significantly reduced unesterified cholesterol and unesterified/total cholesterol ratio. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate (CER), two measures of the efficiency of the esterification process, were reduced by 29% and 16%, respectively, in the plasma of AD patients. Plasma HDL subclass distribution in AD patients was comparable to that of controls but the content of small discoidal preβ-HDL particles was significantly reduced. In agreement with the reduced preβ-HDL particles, cholesterol efflux capacity mediated by the transporters ABCA1 and ABCG1 was reduced in AD patients' plasma. The CSF unesterified to total cholesterol ratio was increased in AD patients, and CSF CER and CEC from astrocytes were significantly reduced in AD patients. In the AD group, a significant positive correlation was observed between plasma unesterified cholesterol and unesterified/total cholesterol ratio with Aβ CSF content.
Taken together our data indicate that cholesterol esterification is hampered in plasma and CSF of AD patients and that plasma cholesterol esterification biomarkers (unesterified cholesterol and unesterified/total cholesterol ratio) are significantly associated to disease biomarkers (i.e., CSF Aβ).
本研究旨在评估阿尔茨海默病（AD）患者血浆和脑脊液（CSF）中的胆固醇酯化和高密度脂蛋白（HDL）亚类。
本研究纳入了 70 名 AD 患者和 74 名认知功能正常的对照者，这些对照者在年龄和性别上与患者相匹配。评估了脂蛋白谱、胆固醇酯化和胆固醇外排能力（CEC）在血浆和 CSF 中的情况。
AD 患者的血浆脂质正常，但未酯化胆固醇和未酯化/总胆固醇比值显著降低。卵磷脂：胆固醇酰基转移酶（LCAT）活性和胆固醇酯化率（CER），这两个衡量酯化过程效率的指标，在 AD 患者的血浆中分别降低了 29%和 16%。AD 患者的血浆 HDL 亚类分布与对照组相似，但小圆盘状前β-HDL 颗粒的含量显著降低。与前β-HDL 颗粒减少一致，AD 患者的血浆 ABCA1 和 ABCG1 介导的胆固醇外排能力降低。AD 患者的 CSF 未酯化胆固醇与总胆固醇比值升高，AD 患者的 CSF CER 和星形胶质细胞的 CEC 显著降低。在 AD 组中，观察到血浆未酯化胆固醇与未酯化/总胆固醇比值与 CSF Aβ 含量呈显著正相关。
综上所述，我们的数据表明，胆固醇酯化在 AD 患者的血浆和 CSF 中受到阻碍，并且血浆胆固醇酯化生物标志物（未酯化胆固醇和未酯化/总胆固醇比值）与疾病生物标志物（即 CSF Aβ）显著相关。
