Staging of Alzheimer-Related Cortical Destruction

Abstract

Currently used criteria for neuropathological diagnosis of Alzheimer's disease (AD) allow only the distinction of fully developed AD or ill-defined cases with less severe pathologic alterations. There is a need for a staging procedure that is able to supplement the currently used criteria, to allow for sufficient differentiation between the initial and intermediate stages of the illness, and to provide a characterization of the degree of involvement in the brain tissue of “nondemented, age-related controls.” The destructive process underlying AD is characterized by a typical distribution pattern of brain changes that is specific with respect to area, lamina, and even cell type. The most conspicuous change is the progressive deposition of abnormal proteins, both between and within the nerve cells. Conventional staining methods to identify these deposits lack sensitivity and specificity. Silver methods (specifically the Gallyas silver-iodide technique for neurofibrillary changes and the Campbell-Switzer silver-pyridin technique for brain amyloid) are by far the best suited to diagnostic work. They are inexpensive, simple to use, and far more reliable. This article describes the patterns of staining typically found with each of these techniques in the brains of patients with progressively severe AD and describes how the specific changes observed can be used as a staging system for diagnostic purposes.