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Correlates and Predictors of Cerebrospinal Fluid Cholesterol Efflux Capacity from Neural Cells, a Family of Biomarkers for Cholesterol Epidemiology in Alzheimer's Disease.

Publication ,  Journal Article
Cipollari, E; Szapary, HJ; Picataggi, A; Billheimer, JT; Lyssenko, CA; Ying, G-S; Shaw, LM; Kling, MA; Kaddurah-Daouk, R; Rader, DJ; Praticò, D ...
Published in: J Alzheimers Dis
2020

BACKGROUND: Basic research has implicated intracellular cholesterol in neurons, microglia, and astrocytes in the pathogenesis of Alzheimer's disease (AD), but there is presently no assay to access intracellular cholesterol in neural cells in living people in the context of AD. OBJECTIVE: To devise and characterize an assay that can access intracellular cholesterol and cholesterol efflux in neural cells in living subjects. METHODS: We modified the protocol for high-density lipoprotein cholesterol efflux capacity (CEC) from macrophages, a biomarker that accesses cholesterol in macrophages in atherosclerosis. To measure cerebrospinal fluid (CSF) CECs from neurons, microglia, and astrocytes, CSF was exposed to, correspondingly, neuronal, microglial, and astrocytic cholesterol source cells. Human neuroblastoma SH-SY5Y, mouse microglial N9, and human astroglial A172 cells were used as the cholesterol source cells. CSF samples were screened for contamination with blood. CSF CECs were measured in a small cohort of 22 individuals. RESULTS: CSF CECs from neurons, microglia, and astrocytes were moderately to moderately strongly correlated with CSF concentrations of cholesterol, apolipoprotein A-I, apolipoprotein E, and clusterin (Pearson's r = 0.53-0.86), were in poor agreement with one another regarding CEC of the CSF samples (Lin's concordance coefficient rc = 0.71-0.76), and were best predicted by models consisting of, correspondingly, CSF phospholipid (R2 = 0.87, p < 0.0001), CSF apolipoprotein A-I and clusterin (R2 = 0.90, p < 0.0001), and CSF clusterin (R2 = 0.62, p = 0.0005). CONCLUSION: Characteristics of the CSF CEC metrics suggest a potential for independent association with AD and provision of fresh insight into the role of cholesterol in AD pathogenesis.

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Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

2020

Volume

74

Issue

2

Start / End Page

563 / 578

Location

Netherlands

Related Subject Headings

  • Predictive Value of Tests
  • Neurons
  • Neurology & Neurosurgery
  • Middle Aged
  • Microglia
  • Male
  • Humans
  • Female
  • Cohort Studies
  • Cholesterol
 

Citation

APA
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ICMJE
MLA
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Cipollari, E., Szapary, H. J., Picataggi, A., Billheimer, J. T., Lyssenko, C. A., Ying, G.-S., … Alzheimer’s Disease Metabolomics Consortium, . (2020). Correlates and Predictors of Cerebrospinal Fluid Cholesterol Efflux Capacity from Neural Cells, a Family of Biomarkers for Cholesterol Epidemiology in Alzheimer's Disease. J Alzheimers Dis, 74(2), 563–578. https://doi.org/10.3233/JAD-191246
Cipollari, Eleonora, Hannah J. Szapary, Antonino Picataggi, Jeffrey T. Billheimer, Catherine A. Lyssenko, Gui-Shuang Ying, Leslie M. Shaw, et al. “Correlates and Predictors of Cerebrospinal Fluid Cholesterol Efflux Capacity from Neural Cells, a Family of Biomarkers for Cholesterol Epidemiology in Alzheimer's Disease.J Alzheimers Dis 74, no. 2 (2020): 563–78. https://doi.org/10.3233/JAD-191246.
Cipollari E, Szapary HJ, Picataggi A, Billheimer JT, Lyssenko CA, Ying G-S, et al. Correlates and Predictors of Cerebrospinal Fluid Cholesterol Efflux Capacity from Neural Cells, a Family of Biomarkers for Cholesterol Epidemiology in Alzheimer's Disease. J Alzheimers Dis. 2020;74(2):563–78.
Cipollari, Eleonora, et al. “Correlates and Predictors of Cerebrospinal Fluid Cholesterol Efflux Capacity from Neural Cells, a Family of Biomarkers for Cholesterol Epidemiology in Alzheimer's Disease.J Alzheimers Dis, vol. 74, no. 2, 2020, pp. 563–78. Pubmed, doi:10.3233/JAD-191246.
Cipollari E, Szapary HJ, Picataggi A, Billheimer JT, Lyssenko CA, Ying G-S, Shaw LM, Kling MA, Kaddurah-Daouk R, Rader DJ, Praticò D, Lyssenko NN, Alzheimer’s Disease Metabolomics Consortium. Correlates and Predictors of Cerebrospinal Fluid Cholesterol Efflux Capacity from Neural Cells, a Family of Biomarkers for Cholesterol Epidemiology in Alzheimer's Disease. J Alzheimers Dis. 2020;74(2):563–578.

Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

2020

Volume

74

Issue

2

Start / End Page

563 / 578

Location

Netherlands

Related Subject Headings

  • Predictive Value of Tests
  • Neurons
  • Neurology & Neurosurgery
  • Middle Aged
  • Microglia
  • Male
  • Humans
  • Female
  • Cohort Studies
  • Cholesterol