Opposite roles of apolipoprotein E in normal brains and in Alzheimer's disease

We have characterized the interaction between apolipoprotein E (apoE) and amyloid beta peptide (A beta) in the soluble fraction of the cerebral cortex of Alzheimer's disease (AD) and control subjects. Western blot analysis with specific antibodies identified in both groups a complex composed of the full-length apoE and A beta peptides ending at residues 40 and 42. The apoE-A beta soluble aggregate is less stable in AD brains than in controls, when treated with the anionic detergent SDS. The complex is present in significantly higher quantity in control than in AD brains, whereas in the insoluble fraction an inverse correlation has previously been reported. Moreover, in the AD subjects the A beta bound to apoE is more sensitive to protease digestion than is the unbound A beta. Taken together, our results indicate that in normal brains apoE efficiently binds and sequesters A beta, preventing its aggregation. In AD, the impaired apoE-A beta binding leads to the critical accumulation of A beta, facilitating plaque formation.