Progression of Alzheimer-Related Neuritic Plaque Pathology in the Entorhinal Region, Perirhinal Cortex and Hippocampal Formation

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Abstract
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.