Apolipoprotein composition of human cerebrospinal fluid lipoproteins varies with APOE genotype

Inheritance of the ε4 allele of the apoliprotein E gene (APOE4) is a risk factor for Alzheimer's disease through unknown mechanisms. ApoE isoforms differ in the number of cysteines they contain. We tested the hypothesis that APOE affects the molecular distribution of apolipoproteins in cerebrospinal fluid (CSF), particularly apoE homodimer and heterodimer formation. A lipoprotein fraction (d < 1.210 g/ml) was isolated from CSF obtained post mortem from individuals of different APOE with or without pathologically-verified AD and analyzed by SDS-PAGE. Under non-reducing conditions, four major protein bands were seen by silver stain in subjects with an APOE3 (APOE3/3 or APOE3/4), while APOE4 homozygotes had only two. The two common bands were apoAI and apoE monomer. The other two bands were reducible dimers: apoE homomdimer and an apoE-apoAII heterodimer. Using immunoblotting, apoAII was shown to exist as either apoAII homodimer or apoE-apoAII complex. Levels of all three apoE-containing apolipoproteins and the proportion of apoAII as homodimer displayed significant APOE allele dosage effects but were not associated with AD. Immunohistochemistry for apoAII showed it was limited to choroid plexus epithelium. There was no immunoreactivity with AD pathological structures, such as that observed with apoE. These data demonstrated an effect of APOE but not AD on apolipoprptein composition, and suggest that apoE-apoAII has different binding properties than apoE alone.