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. 2023 May 20;15(1):95.
doi: 10.1186/s13195-023-01241-6.

Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer's disease

Marta Turri  1 , Elisa Conti  2 , Chiara Pavanello  1 , Francesco Gastoldi  1 , Marcella Palumbo  3 , Franco Bernini  3 , Vittoria Aprea  2 , Francesca Re  4 , Alberto Barbiroli  5 , Davide Emide  5 , Daniela Galimberti  6   7 , Lucio Tremolizzo #  2 , Francesca Zimetti #  3 , Laura Calabresi #  8 ; AGAINST-AD Group
Collaborators, Affiliations

Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer's disease

Marta Turri et al. Alzheimers Res Ther. .

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 Aβ1-42 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 Aβ1-42).

Keywords: Alzheimer’s disease; Apolipoprotein E; Cholesterol efflux; High-density lipoproteins; Lecithin:cholesterol acyltransferase.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
HDL subclass distribution in plasma and CSF of AD patients. Plasma (A, B) and CSF (C, D) HDL were separated by 2-D electrophoresis and detected by anti-apoA-I (A and C) or anti-apoE (B and D) antibodies. Images report representative HDL patterns of one AD patient (AD) and one control (CN). CSF was concentrated 10 folds before analysis
See this image and copyright information in PMC

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