lucifer-yellow and Alzheimer-Disease

Neurofibrillary tangles (NFTs) are composed of insoluble, hyperphosphorylated aggregates of the microtubule-associated protein tau and are present in various neurodegenerative diseases, including Alzheimer's disease (AD). To investigate how tau affects neuronal function during NFT formation and subsequent neurodegeneration, we examined the morphology, spine density, spine type, and spine volume of layer III pyramidal neurons from the prefrontal cortex of mice expressing wild-type human tau (htau) over time. There were no significant alterations in apical dendritic arbor length in 3-, 6-, and 12-month-old htau mice; however, 12-month-old mice exhibited more complex arborization patterns. In addition, we observed a shift in spine morphology with fewer mushroom and more thin spines in both apical and basal dendrites as a function of htau accumulation. Interestingly, there was an overall decrease in volume of spines from 3 to 12 months. However, the volume of mushroom spines decreased from 3 to 6 months and increased from 6 to 12 months. This increase in complexity and branching in 12-month-old mice and the increase of volume of mushroom spines may represent compensatory mechanisms in the remaining intact neurons. As such, the accumulation of phosphorylated tau over time may contribute to the cognitive decline observed in AD by affecting neuronal structure and synaptic properties. Such alterations in dendrites and spines may result in the deterioration of neuronal function observed in AD, and provide a morphologic substrate for the relationship between synaptic integrity and cognitive decline.

Topics: Alzheimer Disease; Animals; Cell Differentiation; Cerebral Cortex; Dendritic Spines; Disease Models, Animal; Humans; Image Cytometry; Isoquinolines; Mice; Mice, Knockout; Mice, Transgenic; Neurofibrillary Tangles; Neurogenesis; Phosphorylation; Prefrontal Cortex; Pyramidal Cells; Staining and Labeling; tau Proteins

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.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Cytoplasmic Granules; Dendrites; Female; Hippocampus; Humans; Isoquinolines; Male; Middle Aged; Neurites