Alzheimer patients and Down patients: cerebral preamyloid deposits differ ultrastructurally and histochemically from the amyloid of senile plaques

Abstract

The preamyloid deposits found in the cerebral grey matter of Alzheimer patients and Down patients following immunostaining with anti-beta-protein antisera are neither birefringent following Congo red staining nor fluorescent after thioflavine S treatment. Further, they contain small amounts of alpha 1-antichymotrypsin, sulfated glycosaminoglycans and complement fraction C3d, but not the P component. As suggested previously, the material accumulated in these deposits may lack the molecular conformation responsible for the properties of amyloid fibrils. To test this hypothesis, we selected cortical samples from 6 Alzheimer and 4 Down patients for an electronmicroscopical study of senile plaques and of preamyloid deposits, both identified by indirect immunogold staining with anti-beta-protein antiserum. We observed the labelling of 4-8 nm wide amyloid fibrils in the plaque cores and of extracellular electrondense, flaky and irregularly distributed material in the preamyloid deposits. In the latter, amyloid fibrils were very rarely detected. These findings support the view that preamyloid deposits mostly contain amyloid precursors that are not yet organized in fibrils.