Dendritic pathology of granule cells in Alzheimer's disease is unrelated to neuritic plaques

Abstract

Neuritic plaques are the histologic hallmark of Alzheimer's disease (AD); however, the extent to which they are injurious to neurons is unclear. In order to investigate this problem, we intracellularly filled human dentate granule cells with Lucifer yellow in a lightly fixed slice preparation and studied the relationships between their dendrites and neuritic plaques. After counterstaining for plaques and drawing the filled granule cell dendrites, we found that there were significant differences in the morphology of dendrites in control and AD cases; granule cell dendrites from Alzheimer's cases were generally shorter, branched less profusely, and had fewer spines than those from age matched controls. Surprisingly, when dendrites traveled into plaques, they still bore spines and their morphology was distinct from that of the amyloid-stained dystrophic neurites surrounding them. Furthermore, within AD cases we found no significant differences between dendrites that were located directly beneath or passing through plaques and those that were located in plaque-free regions. We conclude that granule cell dendrites are not an integral component of plaques within their dendritic fields and that neuritic plaques have no direct effect on granule cells in the dentate gyrus.