Processing of apolipoprotein E in cerebrospinal fluid of patients with Alzheimer's disease

As apolipoprotein E (apoE) allele 4 is a risk factor for late-onset Alzheim er disease (AD), the absolute levels of apoE isoforms were studied in CSF a nd serum of both control and AD patients by means of quantitative 2D gel el ectrophoresis, after calibration with recombinant human apoE. In both contr ol and AD patients, the apoE pattern in CSF was much more complex than in s erum, due to a putative partially processed precursor for each apoE isoform and a higher degree of sialation. This complexity of processing in control patients was not affected by age or apoE genotype. In AD patients, age wea kly correlated with complexity of apoE processing whereas disease severity had no effect. However, processing in CSF from AD apoE3.3 patients was much more prominent than in other AD apoE genotypes or controls. Total CSF leve ls of apoE in AD patients were lower than in control patients and were not affected by age. On the other hand no difference was observed between AD an d controls with regard to apoJ and transthyretin levels. The data suggest t hat the pattern of apoE in CSF is much more complex than originally assumed and that apoE3 specific processing of apoE isoforms is present in CSF.