Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer’s disease
Marta Turri, Elisa Conti, Chiara Pavanello, Francesco Gastoldi, Marcella Palumbo, F. Bernini, Vittoria Aprea, Francesca Re, Alberto Barbiroli, Davide Emide, Daniela Galimberti, Lucio Tremolizzo, Francesca Zimetti, Laura Calabresi, AGAINST-AD Group, Simona Andreoni, Ildebrando Appollonio, Fulvio Da Re, Carlo Ferrarese, Aristotelis Karantzoulis, G Negro, Federico Emanuele Pozzi, Giulia Remoli, Benedetta Storti, C Zoia
Abstract
Abstract Objective 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. Methods 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. Results 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 1-42 CSF content. Conclusion 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 1-42 ).