Progression of Alzheimer-related neuritic plaque pathology in the entorhinal region, perirhinal cortex and hippocampal formation

Extracellular deposits of the beta-amyloid protein and intraneuronal neurof ibrillary changes are hallmarks of Alzheimer's disease. Neurofibrillary cha nges in the cell body of neurons are the neurofibrillary tangles, while bet a-amyloid deposits containing dystrophic neurites with neurofibrillary chan ges are called neuritic plaques. beta-Amyloid deposits and neurofibrillary tangles display a sequential accumulation in the cerebral cortex. In the pr esent study, the topographical distribution of beta-amyloid deposits and ne uritic plaques in the entorhinal region, perirhinal cortex and hippocampal formation was investigated in relationship to the amyloid and neurofibrilla ry staging proposed by Braak. The number of subregions displaying beta-amyl oid deposits and neuritic plaques continuously increases in correlation wit h the amyloid stage (for beta-amyloid deposits r = 0.90, p < 0.0001, for ne uritic plaques r = 0.74, p < 0.0001) and neurofibrillary stage (for beta-am yloid deposits r = 0.53, p < 0.0001, for neuritic plaques r = 0.68, p < 0.0 001). Parallel to the advancement in the neurofibrillary stage, early and l ate predilection sites of beta-amyloid deposits and neuritic plaques can be distinguished. The early predilection sites correspond to projection areas of regions which exhibit incipient neurofibrillary tangles. Furthermore, n euritic plaques only occur in the presence of neurofibrillary tangles in th e areas investigated. The findings indicate that neuritic plaques gradually develop in the projection areas of tangle-bearing neurons.