title: ABCA1-Mediated Cholesterol Efflux Capacity to Cerebrospinal Fluid Is Reduced in Patients With Mild Cognitive Impairment and Alzheimer's Disease.
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.
  
  
  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.
authors.affiliation: Department of Medicine, University of Southern California, Los Angeles, CA hyassine@usc.edu.
authors.forename: Hussein N
authors.initials: HN
authors.lastname: Yassine
authors.affiliation: Department of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Qingru
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Molecular Neurology Program, Huntington Medical Research Institutes, Pasadena, CA.
authors.forename: Jiarong
authors.initials: J
authors.lastname: Chiang
authors.affiliation: Department of Medicine, University of Southern California, Los Angeles, CA Department of Neurology, University of Southern California, Los Angeles, CA.
authors.forename: Larissa M
authors.initials: LM
authors.lastname: Petrosspour
authors.affiliation: Molecular Neurology Program, Huntington Medical Research Institutes, Pasadena, CA.
authors.forename: Alfred N
authors.initials: AN
authors.lastname: Fonteh
authors.affiliation: Department of Neurology, University of Southern California, Los Angeles, CA.
authors.forename: Helena C
authors.initials: HC
authors.lastname: Chui
authors.affiliation: Molecular Neurology Program, Huntington Medical Research Institutes, Pasadena, CA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Harrington
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000134:cerebrospinal fluid* / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D000818:Animals; D001692:Biological Transport; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D002460:Cell Line; D002784:Cholesterol / Q000134:cerebrospinal fluid*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D006224:Cricetinae; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D010713:Phosphatidylcholines / Q000134:cerebrospinal fluid; D014162:Transfection
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D015415:Biomarkers; D010713:Phosphatidylcholines; D002784:Cholesterol
keywords: ABCA1 transporters; Alzheimer's disease; cerebrospinal fluid; cholesterol efflux