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

Cinzia Marchi, Maria Pia Adorni, Paolo Caffarra, Nicoletta Ronda, Marco Spallazzi, Federica Barocco, Daniela Galimberti, Franco Bernini, Francesca Zimetti

Research output: Contribution to journalArticlepeer-review

Abstract

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 apo?4 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.- Marchi, C., M. P. Adorni, P. Caffarra, N. Ronda, M. Spallazzi, F. Barocco, D. Galimberti, F. Bernini, and F. Zimetti. ABCA1- and ABCG1-mediated cholesterol efflux capacity of cerebrospinal fluid is impaired in Alzheimer's disease. J. Lipid Res. 2019. 60: 1449-1456.

Original languageEnglish
Pages (from-to)1449-1456
Number of pages8
JournalJournal of Lipid Research
Volume60
Issue number8
DOIs
Publication statusPublished - Jan 1 2019

Keywords

  • Apolipoprotein A-I
  • Apolipoprotein E
  • Apolipoprotein E4
  • Apolipoproteins
  • ATP-binding cassette A1
  • ATP-binding cassette G1

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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