Limited effect of neuritic plaques on neuronal density in the hippocampal CA1 area of Alzheimer patients

Neurofibrillary tangles (NFTs) and neuritic plaques (NPs) are the classic n europathological hallmarks of Alzheimer disease (AD). It is generally assum ed that the pathogenic process of AD could start by local neurotoxicity ind uced by the beta-amyloid core of plaques, followed by the appearance of NFT s and eventually cell death. To determine whether or not local neurotoxicit y around NPs is indeed a major pathogenetic mechanism, we used an image ana lysis system to measure the neuronal density around Bodian-stained NPs in t he hippocampal CA1 area of eight AD patients. Neuronal density, as measured within two arbitrary concentric circles around NPs with a radius of 74 and 123.5 mu m, respectively, was on average 19% and 16% lower than the densit y in similar control circles without NPs in the same section. Furthermore, neuronal density around NPs was inversely related to their size. To investi gate the impact of such a local reduction in cell density around NPs on the entire CA1 area, we also determined the proportion of the CA1 covered by t he NPs and the arbitrary concentric circles around them. This appeared to b e 16.3% of the total CAI area, which means that the negative effect of NPs on the cell density can only explain 2.6% of cell death in the entire CA1 a rea. In conclusion, this study suggests that although NPs have a local nega tive effect on neighboring neurons, their contribution to the strong decrea se in CA1 cell numbers is limited.