MORPHOLOGY AND DISTRIBUTION OF PLAQUE AND RELATED DEPOSITS IN THE BRAINS OF ALZHEIMERS-DISEASE AND CONTROL CASES - AN IMMUNOHISTOCHEMICAL STUDY USING AMYLOID BETA-PROTEIN ANTIBODY

Abstract

A monoclonal antibody (4D12/2/6) to a synthetic peptide consisting of residues 8-17 of the amyloid .beta.-protein of Alzheimer''s disease was used in an immunohistochemical study to investigate the localization of .beta.-protein immunoreactivity in neuritic plaques in the brains of 20 cases with Alzheimer''s disease and a similar number on nonAlzheimer controls. The morphology and distribution of immunoreactive plaque-like lesions and the sensitivity of immunostaining were assessed both with and without formic acid pretreatment of the sections, and these results were compared with those obtained using conventional Congo red and silver impregnation staining methods. Congo read and immunostaining without formic acid pretreatment mainly stained the core desposits of amyloid in compact plaques, whereas the silver stain could also detect numerous diffuse plaques. Immunostaining with formic acid pretreatment was the most sensitive technique, and this revealed many additional immunoreactive lesions which were impossible or difficult to detect with the other staining methods. These additional lesions included variable sized areas of faint granular staining with little evidence of amyloid deposition of degenerating neurites that are presumed to be very early stages in plaque development. Far fewer immunoreactive lesions were observed in the nonAlzheimer controls. It is concluded that an abundant presence of anti-.beta.-protein immunoreactive plaque lesions througout the cortex and subcortical gray matter structures is typical of Alzheimer''s disease even when only moderate numbers of plaques can be detected by Congo red or silver stain. This immunostaining procedure with a specific monoclonal antibody for .beta.-protein may be very useful for the postmortem diagnosis of Alzheimer''s disease.