Influence of double (APP and PS1) mutations on sprouting in the hippocampus following entorhinal cortex lesions in mice and the effects of estrogen

Abstract

In Alzheimer's disease, the main component of amyloid deposits is a 39–43 amino acid peptide referred to as amyloid peptide or A β. A crucial issue in the study of this disorder is to define the sequence of events that lead to amyloid deposition. In the present study, a new approach was developed that allows to specifically solubilize A β peptide trapped within amyloid deposits and to quantify its amount by dot-blot immunoassay. The present method also permits to isolate components tightly bound to A β and that are likely to catalyze its aggregation. Biochemical A β quantitation was performed in 4 Brodmann areas from 17 elderly individuals exhibiting different degrees of amyloidosis. In parallel, classical neuropathology was done by histochemical and immunohistochemical methods. A β amounts (pmol) were correlated to the number of amyloid deposits determined by neuropathology showing high statistical significance. Moreover, amyloid-binding proteins including apolipoprotein E and heparan sulfate proteoglycans were also found associated to A β in the amyloid preparation. The present biochemical procedure is a new and reliable method to quantify amyloid deposition in brain. Furthermore, it allows to detect amyloid-associated components such as apolipoprotein E, that may be involved in the pathological process of amyloidogenesis.