Potential role of apolipoprotein-E in fibrillogenesis.
Immunohistochemical and biochemical studies have demonstrated several different proteins in amyloid deposits that are not intrinsic components of the fibril itself but may play a role in their deposition and fibril formation. We compared the distribution of several amyloid-associated proteins, ie, amyloid P component, apolipoprotein-E, apolipoprotein-J, and vitronectin, in the deposits of several different amyloids, in particular light chain amyloid, with those in the deposits of nonamyloid monoclonal immunoglobulin, which may be considered a form of preamyloid disease. Although 100% of amyloid specimens (7 amyloid A, 15 immunoglobulin light chain, and 1 transthyretin) had amyloid P component and 100% had apolipoprotein-E (2 amyloid A, 10 immunoglobulin light chain, and 1 transthyretin) co-localized with the primary amyloid protein, none of the monoclonal nonamyloid cases (14 light chain deposition disease and 6 light and heavy chain deposition disease) had amyloid P component and only 1 of 11 had apolipoprotein-E. On the other hand, staining for apolipoprotein-J and vitronectin was positive in 100% of cases of amyloid and nonamyloid monoclonal deposits. The association between the presence of apolipoprotein-E and amyloid P component in the fibrillar form of monoclonal light chain deposits and their absence in the nonfibrillar form of deposits suggest a role for these proteins in the process of fibrillogenesis. This lends support for the previously proposed concept that apolipoprotein-E functions as a pathological chaperone by altering the conformation of amyloidogenic proteins.
Gallo
G
G
Department of Pathology, New York University Medical Center, NY 10016.
Wisniewski
T
T
Choi-Miura
N H
NH
Ghiso
J
J
Frangione
B
B
D000686:Amyloidosis / Q000276:immunology*; D001053:Apolipoproteins / Q000032:analysis / Q000502:physiology; D001057:Apolipoproteins E / Q000032:analysis* / Q000502:physiology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis; D007147:Immunoglobulin Light Chains / Q000032:analysis
D001053:Apolipoproteins; D001057:Apolipoproteins E; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains