DIFFERENTIAL PATTERN OF BETA-AMYLOID, AMYLOID PRECURSOR PROTEIN AND APOLIPOPROTEIN-E EXPRESSION IN CORTICAL SENILE PLAQUES

Regional differences in senile plaques immunostained by antibodies aga inst beta-amyloid A4 (beta-A4), amyloid precursor protein 695 (APP) an d apolipoprotein E (ape E) were studied in the hippocampus and the ent orhinal, temporal and occipital cortices both quantitatively and semiq uantitatively with respect to the laminar cortical distribution of the plaques. These patterns were related to the staging of Alzheimer's di sease 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 o f plaques visualized by the different antibodies were found. In contra st, there was a striking difference in neocortical regions. Here, sign ificantly 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-positi ve plaques were found in the isocortical layers III and V and in the e ntorhinal pre-alpha, pre-gamma, pri-alpha and pri-beta layers. The pre ferentially affected area, showing plaques positive for all three anti bodies, was the entorhinal-hippocampal circuit with early affection of CA 1, which represents the direct and indirect target of the entorhin al neurons of the upper layers. Therefore, we suggest that plaques wit h dystrophic neurites, positive for APP, seem to be generated secondar ily in afferent areas such as the hippocampus, which is the main affer ent target of the entorhinal region. Diffuse plaques, negative for APP and apo E, are virtually absent in the CA 1 and seem to originate ind ependently of afferent neuronal dysfunction, as indicated by neurofibr illary tangles.