Apolipoprotein J and Alzheimer's amyloid beta 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.
Matsubara
E
E
Department of Pathology, New York University Medical Center, NY 10016, USA.
Soto
C
C
Governale
S
S
Frangione
B
B
Ghiso
J
J
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D002918:Chymotrypsin / Q000378:metabolism; D002942:Circular Dichroism; D051152:Clusterin; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007122:Immunoelectrophoresis; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011228:Prealbumin / Q000494:pharmacology; D012995:Solubility; D014357:Trypsin / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D018832:Molecular Chaperones; D010446:Peptide Fragments; D011228:Prealbumin; D002918:Chymotrypsin; D014357:Trypsin