Faculty Bibliography

We report the clinical data and results of biochemical studies of amyloid in a postpartum patient. The amyloidosis was not associated with myeloma, and immunopathologic examination of the amyloid deposits gave inconclusive results. Biochemical analysis of the deposits proved that the amyloid protein JUN was derived from the variable region of the kappa light chain subgroup III and is homologous to a rarely expressed protein POM, which was previously shown to have rheumatoid factor activity. The significance of this association and the diagnostic problems associated with certain cases of amyloid derived from immunoglobulin light chain (type AL) are discussed

We performed immunocytochemical staining to study the distribution of serum protease inhibitors in cerebral and systemic amyloid deposits. In beta-protein amyloid deposits in Alzheimer's disease, Down's syndrome, age-related cerebral amyloidosis, sporadic cerebral amyloid angiopathy and hereditary cerebral hemorrhage with amyloidosis of Dutch origin, antibody to alpha 1-antichymotrypsin (ACT) stains senile plaques and vascular deposits. Immature plaques or preamyloid deposits, identified by their positive staining for beta-protein and negative staining for Congo red, which represents the earliest recognizable stages of amyloid deposition, are also labeled. We did not detect ACT in other chemically different forms of cerebral and systemic amyloid. None of the other inhibitors in this study, i.e. antithrombin III and alpha 2-macroglobulin, was detected in the amyloid deposits. Neurons and glial cells throughout the central nervous system in normal and amyloid-containing brains also bind ACT antibody. The results emphasize the close association of ACT with one type of cerebral amyloid (beta-amyloid diseases) as well as the failure to detect such an association in other chemically different forms of cerebral and systemic amyloids

The amyloid fibrils deposited in cerebral vessel walls and senile plaques in Alzheimer's disease are polymeric forms of a 4 kDa fragment produced by proteolysis of a putative precursor protein (APP). Using antibodies to several fragments of the deduced precursor, we were able to demonstrate the presence of APP in senile plaques, brain extracts and cerebrospinal fluid. Membrane-associated APP is detected as a group of 105-135 kDa proteins while soluble APP is predominantly 105 kDa, does not react with an anti C-terminal antibody, and is 10 kDa shorter than the membrane-bound APP. Amino terminal sequence of the tissue 105 kDa protein indicates that APP begins at residue 18 of the cDNA sequence. These findings imply that i) two forms of APP are detected: membrane-bound and secreted, and ii) APP can be processed in situ