Differential pattern of beta-amyloid, amyloid precursor protein and apolipoprotein E expression in cortical senile plaques

Regional differences in senile plaques immunostained by antibodies against beta-amyloid A4 (beta-A4), amyloid precursor protein 695 (APP) and apolipoprotein E (ape E) were studied in the hippocampus and the entorhinal, temporal and occipital cortices both quantitatively and semiquantitatively with respect to the laminar cortical distribution of the plaques. These patterns were related to the staging of Alzheimer's disease in regard to the distribution of neurofibrillary tangles [Braak and Braak (1991) Acta Neuropathol 82: 239-259]. In the hippocampus and especially in sector CA 1, no significant differences in the number of plaques visualized by the different antibodies were found. In contrast, there was a striking difference in neocortical regions. Here, significantly higher numbers of plaques positive for beta-A4 than that for APP and apo E were present in all stages, except in the stages I and VI, and for apo E in stage II. The highest densities of beta-A4-positive plaques were found in the isocortical layers III and V and in the entorhinal pre-alpha, pre-gamma, pri-alpha and pri-beta layers. The preferentially affected area, showing plaques positive for all three antibodies, was the entorhinal-hippocampal circuit with early affection of CA 1, which represents the direct and indirect target of the entorhinal neurons of the upper layers. Therefore, we suggest that plaques with dystrophic neurites, positive for APP, seem to be generated secondarily in afferent areas such as the hippocampus, which is the main afferent target of the entorhinal region. Diffuse plaques, negative for APP and apo E, are virtually absent in the CA 1 and seem to originate independently of afferent neuronal dysfunction, as indicated by neurofibrillary tangles.