Apolipoprotein J and Alzheimer's amyloid β solubility

Apolipoprotein J (apoJ) has been found associated with soluble amyloid beta (sA beta) in plasma and cerebrospinal fluid in normal individuals and co-deposited with fibrillar A beta in Alzheimer's cerebrovascular and parenchymal lesions. Although studies in vitro and in vivo indicate that apoJ is a major carrier protein for sA beta, its role in the fibrillogenesis process is not known. We report herein that apoJ in its native high-density lipoprotein lipidic environment is fully active to interact with A beta peptides. Furthermore, apoJ prevents aggregation and polymerization of synthetic A beta in vitro. The interaction was stable for at least 14 days at 37 degrees C in physiologic buffers, and the peptide retrieved after complex dissociation at low pH retained its inherent aggregation properties. In addition, the binding to apoJ protects synthetic A beta from proteolytic degradation; both A beta 1-42 and A beta 1-40 were more resistant to proteolysis by trypsin and chymotrypsin when complexed to apoJ. The data suggest that the interaction may preclude sA beta aggregation in biological fluids and point to a protecting role of apoJ for complexed A beta species.