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J Am Heart Assoc. 2016 Feb 12;5(2). pii: e002886. doi: 10.1161/JAHA.115.002886.

ABCA1-Mediated Cholesterol Efflux Capacity to Cerebrospinal Fluid Is Reduced in Patients With Mild Cognitive Impairment and Alzheimer's Disease.

Author information

1
Department of Medicine, University of Southern California, Los Angeles, CA hyassine@usc.edu.
2
Department of Medicine, University of Southern California, Los Angeles, CA.
3
Molecular Neurology Program, Huntington Medical Research Institutes, Pasadena, CA.
4
Department of Medicine, University of Southern California, Los Angeles, CA Department of Neurology, University of Southern California, Los Angeles, CA.
5
Department of Neurology, University of Southern California, Los Angeles, CA.

Abstract

BACKGROUND:

Animal and human studies indicate that ABCA1-mediated cholesterol transport is important in Alzheimer's disease (AD). We hypothesized that the efficiency of cerebrospinal fluid (CSF) to facilitate ABCA1-mediated cholesterol efflux would be reduced in participants with mild cognitive impairment (MCI) or AD compared with cognitively healthy participants.

METHODS AND RESULTS:

CSF was collected from a cross-sectional study of cognitively healthy participants (n=47) and participants with MCI (n=35) or probable AD (n=26).The capacity of CSF to mediate cholesterol transport was assessed using a BHK cell line that can be induced to express the ABCA1 transporter. ABCA1-mediated cholesterol efflux capacity was 30% less in participants with MCI or AD compared with cognitively healthy participants (P<0.001 for both). Cholesterol efflux capacity correlated with CSF cholesterol content (r=0.37, P<0.001). CSF phosphatidylcholine decreased in participants with MCI and AD compared with cognitively healthy participants (9% less in MCI and 27% less in AD compared with cognitively healthy participants, P=0.01) and correlated with CSF efflux capacity (r=0.3, P=0.001). CSF sphingomyelin also correlated with the efflux capacity (r=0.24, P=0.02). Concentrations of CSF apoA-I and apoE did not significantly correlate with measures of efflux capacity.

CONCLUSIONS:

In people with MCI and AD, the capacity of CSF to facilitate ABCA1-mediated cholesterol efflux is impaired. This lesser cholesterol efflux in MCI supports a pathophysiological role for ABCA1-mediated cholesterol transport in early neurodegeneration.

KEYWORDS:

ABCA1 transporters; Alzheimer's disease; cerebrospinal fluid; cholesterol efflux

PMID:
26873692
PMCID:
PMC4802440
DOI:
10.1161/JAHA.115.002886
[Indexed for MEDLINE]
Free PMC Article

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