Phospho-Tau Accumulation and Structural Alterations of the Golgi Apparatus of Cortical Pyramidal Neurons in the P301S Tauopathy Mouse Model

The Golgi apparatus (GA) is a highly dynamic organelle involved in the processing and sorting of cellular proteins. In Alzheimer's disease (AD), it has been shown to decrease in size and become fragmented in neocortical and hippocampal neuronal subpopulations. This fragmentation and decrease in size of the GA in AD has been related to the accumulation of hyperphosphorylated tau. However, the involvement of other pathological factors associated with the course of the disease, such as the extracellular accumulation of amyloid-beta (A beta) aggregates, cannot be ruled out, since both pathologies are present in AD patients. Here we use the P301S tauopathy mouse model to examine possible alterations of the GA in neurons that overexpress human tau (P301S mutated gene) in neocortical and hippocampal neurons, using double immunofluorescence techniques and confocal microscopy. Quantitative analysis revealed that neurofibrillary tangle (NFT)-bearing neurons had important morphological alterations and reductions in the surface area and volume of the GA compared with NFT-free neurons. Since in this mouse model there are no A beta aggregates typical of AD, the present findings support the idea that the progressive accumulation of phospho-tau is associated with structural alterations of the GA, and that these changes may occur in the absence of A beta pathology.