title: Morphometric alterations of Golgi apparatus in Alzheimer's disease are related to tau hyperphosphorylation.
abstract: The Golgi apparatus (GA) is a highly dynamic organelle, which is mainly involved in the post-translational processing and targeting of cellular proteins and which undergoes significant morphological changes in response to different physiological and pathological conditions. In the present study, we have analyzed the possible alterations of GA in neurons from the temporal neocortex and hippocampus of Alzheimer's disease (AD) patients, using double immunofluorescence techniques, confocal microscopy and 3D quantification techniques. We found that in AD patients, the percentage of temporal neocortical and CA1 hippocampal pyramidal neurons with a highly altered GA is much higher (approximately 65%) in neurons with neurofibrillary tangles (NFT) than in NFT-free neurons (approximately 6%). Quantitative analysis of the surface area and volume of GA elements in neurons revealed that, compared with NFT-free neurons, NFT-bearing neurons had a reduction of approximately one half in neocortical neurons and one third in CA1 neurons. In both regions, neurons with a pre-tangle stage of phospho-tau accumulation had surface area and GA volume values that were intermediate, that is, between those of NFT-free and NFT-bearing neurons. These findings support the idea that the progressive accumulation of phospho-tau is associated with structural alterations of the GA including fragmentation and a decrease in the surface area and volume of GA elements. These alterations likely impact the processing and trafficking of proteins, which might contribute to neuronal dysfunction in AD.
authors: Instituto Cajal, CSIC, Madrid, Spain; Laboratorio Cajal de Circuitos Corticales (CTB), Universidad Politécnica de Madrid, Madrid, Spain.
authors: Alejandro
authors: A
authors: Antón-Fernández
authors: Instituto Cajal, CSIC, Madrid, Spain; Laboratorio Cajal de Circuitos Corticales (CTB), Universidad Politécnica de Madrid, Madrid, Spain.
authors: Guillermo
authors: G
authors: Aparicio-Torres
authors: Instituto Cajal, CSIC, Madrid, Spain; Laboratorio Cajal de Circuitos Corticales (CTB), Universidad Politécnica de Madrid, Madrid, Spain.
authors: Silvia
authors: S
authors: Tapia
authors: Instituto Cajal, CSIC, Madrid, Spain; Laboratorio Cajal de Circuitos Corticales (CTB), Universidad Politécnica de Madrid, Madrid, Spain; CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Spain.
authors: Javier
authors: J
authors: DeFelipe
authors: Instituto Cajal, CSIC, Madrid, Spain; Laboratorio Cajal de Circuitos Corticales (CTB), Universidad Politécnica de Madrid, Madrid, Spain; Department of Cell Biology, Complutense University, Madrid, Spain. Electronic address: amunozc@bio.ucm.es.
authors: Alberto
authors: A
authors: Muñoz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000473:pathology*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008875:Middle Aged; D019579:Neocortex / Q000473:pathology*; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D013048:Specimen Handling; D013997:Time Factors
keywords: Dementia; Human hippocampus; Human neocortex; Microtubules; Neurofibrillary tangles; Taupathy