Apolipoprotein E allelic influence on human cerebrospinal fluid apolipoproteins

The major apolipoproteins (apo)on human cerebrospinal fluid lipoproteins ar e apoA-I and apoE, Given the association between inheritance of the epsilon 4 allele of the apoE gene (APOE4) and increased susceptibility to Alzheime r's disease, we tested the hypothesis that cerebrospinal fluid apolipoprote ins may be influenced by APOE genotype and Alzheimer's disease. Lipoprotein fractions (d < 1.210 g/ml) were isolated from cerebrospinal fluid obtained from individuals with different APOE genotypes and with or without patholo gically verified Alzheimer's disease, Apolipoproteins were separated by SDS -polyacrylamide gel electrophoresis and identified by silver nitrate staini ng, Western blotting, and N-terminal amino acid sequencing, Four protein sp ecies were detected by silver nitrate staining in subjects with an APOE3 al lele: apoA-I, apoE monomer, apoE-apoA-II heterodimer, and apoE homodimer, I n APOE4 homozygotes, only apoA-I and apoE monomer were detected. ApoA-II ho modimer was demonstrated in all subjects by Western blotting. The relative levels of apoE- and apoA-II-containing apolipoproteins correlated with APOE genotype but were not altered by Alzheimer's disease, In contrast to apoE, no apoA-II immunoreactivity was observed with pathological structures in A lzheimer's disease brain. These differences in cerebrospinal fluid apolipop roteins may influence lipoprotein trafficking and may be an element in the stratification of risk for Alzheimer's disease with APOE genotype.