No abstract

The staging method proposed by Braak and Braak allows the objective and reliable assessment of Alzheimer-related neurofibrillary pathology. Originally the method was designed for 100-µm thick sections. However, the use of thick sections proved to present difficulties in a routine neuropathology laboratory. In order to adapt the staging method for thin paraffin-embedded sections, we performed an inter- and intrarater study analysing the reliability of the staging method in thin sections. Statistical analysis of the data provided by six independent examiners in two rating sessions reveal kappa values of 0.6–0.8 for both the interrater and the intrarater reliability. The average rate of mistake of the examiners was rarely bigger than a half stage. We conclude that the adapted staging method in thin sections is strongly reliable and we recommend it for staging purposes in institutions where the preparation of thick sections would be difficult.

The staging method proposed by Braak and Braak is based on the sequential accumulation of neurofibrillary pathology in the cerebral cortex. Unlike the currently used diagnostic criteria for Alzheimer''s disease (AD) it does not take into consideration the age of the patients and whether they were demented or not for the establishment of the pathological stage of the disease. To examine the interobserver reliability of the method we performed an inter- and intrarater study using the Braak staging method in 41 brains. The agreement between the examiners and between the diagnoses of the same examiner at different times was almost perfect, the kappa statistics reaching values above 0.90. These findings indicate that the staging, relying on the differential distribution of neuritic pathology in the brain in AD, is a reliable and reproducible method for the description of AD-related pathology. This makes it suitable for brain-banking and research purposes.

Extracellular deposits of the β-amyloid protein and intraneuronal neurofibrillary changes are hallmarks of Alzheimer’s disease. Neurofibrillary changes in the cell body of neurons are the neurofibrillary tangles, while β-amyloid deposits containing dystrophic neurites with neurofibrillary changes are called neuritic plaques. β-Amyloid deposits and neurofibrillary tangles display a sequential accumulation in the cerebral cortex. In the present study, the topographical distribution of β-amyloid deposits and neuritic plaques in the entorhinal region, perirhinal cortex and hippocampal formation was investigated in relationship to the amyloid and neurofibrillary staging proposed by Braak. The number of subregions displaying β-amyloid deposits and neuritic plaques continuously increases in correlation with the amyloid stage (for β-amyloid deposits r = 0.90, p < 0.0001, for neuritic plaques r = 0.74, p < 0.0001) and neurofibrillary stage (for β-amyloid deposits r = 0.53, p < 0.0001, for neuritic plaques r = 0.68, p < 0.0001). Parallel to the advancement in the neurofibrillary stage, early and late predilection sites of β-amyloid deposits and neuritic plaques can be distinguished. The early predilection sites correspond to projection areas of regions which exhibit incipient neurofibrillary tangles. Furthermore, neuritic plaques only occur in the presence of neurofibrillary tangles in the areas investigated. The findings indicate that neuritic plaques gradually develop in the projection areas of tangle-bearing neurons.