ABCA1- and ABCG1-mediated cholesterol efflux capacity of cerebrospinal fluid is impaired in Alzheimer's disease.

Autor:	Marchi C; Department of Food and Drug University of Parma, Parma, Italy., Adorni MP; Department of Food and Drug University of Parma, Parma, Italy., Caffarra P; Department of Medicine and Surgery, Section of Neurology University of Parma, Parma, Italy.; Alzheimer Center Briolini Hospital, Gazzaniga, Bergamo, Italy., Ronda N; Department of Food and Drug University of Parma, Parma, Italy fbernini@unipr.it nicoletta.ronda@unipr.it., Spallazzi M; Department of Medicine and Surgery, Section of Neurology University of Parma, Parma, Italy., Barocco F; Department of Medicine and Surgery, Section of Neurology University of Parma, Parma, Italy., Galimberti D; Department of Biomedical, Surgical and Dental Sciences, Dino Ferrari Center, University of Milano, Milano, Italy.; Neurodegenerative Diseases Unit Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milano, Italy., Bernini F; Department of Food and Drug University of Parma, Parma, Italy fbernini@unipr.it nicoletta.ronda@unipr.it., Zimetti F; Department of Food and Drug University of Parma, Parma, Italy.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2019 Aug; Vol. 60 (8), pp. 1449-1456. Date of Electronic Publication: 2019 Jun 05.
DOI:	10.1194/jlr.P091033
Abstrakt:	HDL-like particles in human cerebrospinal fluid (CSF) promote the efflux of cholesterol from astrocytes toward the neurons that rely on this supply for their functions. We evaluated whether cell cholesterol efflux capacity of CSF (CSF-CEC) is impaired in Alzheimer's disease (AD) by analyzing AD ( n = 37) patients, non-AD dementia (non-AD DEM; n = 16) patients, and control subjects ( n = 39). As expected, AD patients showed reduced CSF Aβ 1-42, increased total and phosphorylated tau, and a higher frequency of the apoε4 genotype. ABCA1- and ABCG1-mediated CSF-CEC was markedly reduced in AD (-73% and -33%, respectively) but not in non-AD DEM patients, in which a reduced passive diffusion CEC (-40%) was observed. Non-AD DEM patients displayed lower CSF apoE concentrations (-24%) compared with controls, while apoA-I levels were similar among groups. No differences in CSF-CEC were found by stratifying subjects for apoε4 status. ABCG1 CSF-CEC positively correlated with Aβ 1-42 ( r = 0.305, P = 0.025), while ABCA1 CSF-CEC inversely correlated with total and phosphorylated tau ( r = -0.348, P = 0.018 and r = -0.294, P = 0.048, respectively). The CSF-CEC impairment and the correlation with the neurobiochemical markers suggest a pathophysiological link between CSF HDL-like particle dysfunction and neurodegeneration in AD. (Copyright © 2019 Marchi et al.)
Databáze:	MEDLINE
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