Faculty Bibliography

Apolipoprotein E (Apo E) has been shown to be closely associated with beta amyloid in Alzheimer's disease (AD) brain. In the present study, we have found strong Apo E immunoreactivity in the amyloid cores of senile plaques (SP) in the various brain regions examined. However, Apo E immunoreactivity in diffuse plaques varied distinctly and was strong within numerous cerebellar and cortical diffuse plaques, and absent or very weak within diffuse plaques in the striatum/thalamus. This distribution of Apo E immunoreactivity in SP correlates with the occurrence of small amounts of fibrillar amyloid in diffuse plaques that has been described in the cerebral and cerebellar cortex, but not in the basal ganglia. These results show that Apo E may be associated with sites of beta amyloid fibril formation in diffuse plaques in AD brain, but they also suggest that factors other than Apo E, probably local, may influence fibrillogenesis

Alzheimer's disease is characterized by the deposition of beta-protein (A beta) as amyloid. Recently, it was found that A beta is a normal component of serum and cerebrospinal fluid. Synthetic peptides homologous to A beta form amyloid-like fibrils spontaneously in water or physiological solutions. Using a peptide homologous to A beta 1-40, we find that fibril formation is inhibited by the presence of cerebrospinal fluid

The amyloid fibrils deposited in Alzheimer's neuritic plaque cores and cerebral blood vessels are mainly composed of aggregated forms of a unique peptide, 39-42 amino acids long, named amyloid beta (A beta). A similar, although soluble, A beta ('sA beta') has been identified in cerebrospinal fluid, plasma and cell supernatants, indicating that it is normally produced by proteolytic processing of its precursor protein, amyloid precursor protein (APP). Using direct binding experiments we have isolated and characterized an 80 kDa circulating protein that specifically interacts with a synthetic peptide identical with A beta. The protein was unmistakably identified as SP-40,40 or ApoJ, a cytolytic inhibitor and lipid carrier, by means of amino acid sequence and immunoreactivity with specific antibodies. Immunoprecipitation with anti-SP-40,40 retrieved soluble A beta from cerebrospinal fluid, indicating that the interaction occurs in vivo

Apolipoprotein E (apo E) is associated with Alzheimer's beta-amyloid (A beta) in senile plaques. A beta is now known to be a normal soluble peptide (sA beta) found in the cerebrospinal fluid (CSF) and other biological fluids. We have used synthetic A beta peptides bound to affinity membranes in order to determine whether apo E or any other amyloid associated protein will bind to these membranes, when they are bathed in CSF. Under these conditions apo E, as well as another apolipoprotein, apolipoprotein J (Apo J), bound to the membranes. Using ELISA and ligand binding studies, we found a high avidity binding of A beta peptides to apo E. This suggests that apo E, as well as other related proteins may bind not only amyloid A beta but also sA beta. This interaction may be critical in amyloid formation

Immunohistologic studies of tissue sections obtained from patients with type 1 or type 2 lattice corneal dystrophy, polymorphic amyloid degeneration, or gelatinous amyloid degeneration were performed by using a monoclonal antibody raised to a chymotryptic fragment inclusive of the carboxy-terminal half of plasma gelsolin, and also with a series of polyclonal antibodies specific for synthetic peptides corresponding to immunogenic epitopes of gelsolin. These epitopes are parts of sequences at the amino- and carboxy-terminal ends of gelsolin, as well as adjacent to and inclusive of the codon 187 mutant 7-11 kD fragment that has been shown to be the subunit protein of amyloid fibrils occurring systemically in patients affected by Finnish type familial amyloidosis. These antibodies were also tested on tissue sections obtained from patients with granular and macular corneal dystrophy, corneal wounds, and normal control corneas. Specificity of staining was established by absorption with gelsolin purified from plasma, or the appropriate synthetic peptide. Gelsolin immunoreactivity was detected in the conjunctival and skin amyloid in familial amyloidosis by using familial amyloid (Finnish type) antibody. In other types of corneal amyloid, including lattice dystrophy type 1, immunoreactivity with gelsolin and synthetic peptides was observed adjacent to the deposits, but rarely within them. In macular dystrophy, variable staining of the deposits could result from the association of subunit proteins with glycosaminoglycans