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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / cerebrospinal fluid*
  • ATP Binding Cassette Transporter 1 / genetics
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnosis
  • Animals
  • Biological Transport
  • Biomarkers / cerebrospinal fluid
  • Case-Control Studies
  • Cell Line
  • Cholesterol / cerebrospinal fluid*
  • Cognitive Dysfunction / cerebrospinal fluid*
  • Cognitive Dysfunction / diagnosis
  • Cricetinae
  • Cross-Sectional Studies
  • Down-Regulation
  • Female
  • Humans
  • Male
  • Phosphatidylcholines / cerebrospinal fluid
  • Transfection


  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • Biomarkers
  • Phosphatidylcholines
  • Cholesterol