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

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. © 2016 the authors.