Golgi Apparatus and Protein Trafficking in Alzheimer's Disease

What is it about?

Alzheimer’s disease (AD) is a progressive degeneration of the brain, inducing memory decline, inability in learning, and behavioral alterations, resulting progressively in a marked deterioration of all mental activities and eventually a vegetative state. The main causative factor, however, is still unclear. The implication of amyloid-
, A
PP, tau protein, the selective loss of neurons, the alteration of the synapses, the cytoskeletal changes, and the morphological alterations of the brain capillaries contribute substantially to the pathogenetic profile of the disease, without sufficiently enlightening the initial steps of the pathological procedures. The ultrastructure of the neuronal organelles as well as histochemical studies revealed substantial alterations, primarily concerning mitochondria. In this study, the morphological and morphometric alterations of the Golgi apparatus (GA) are described in the Purkinje cells of the cerebellum in twenty AD brains, studied with electron microscopy. As it is well established, GA has a very important role to play in many procedures such as glycosylation, sulfation, and proteolysis of protein systems, which are synthesized in the endoplasmic reticulum of nerve cells and glia. GA may also play a crucial role in protein trafficking and in misfolding of protein aggregates. In addition, the hyperphosphorylation of tau protein is closely related with the pathology of GA. In AD cases, described in this study, an obvious fragmentation of the cisternae of GA was observed in the Purkinje cells of the vermis and the cerebellar hemispheres. This alteration of GA may be associated with alterations of microtubules, impaired protein trafficking, and dendritic, spinal, and synaptic pathology, since protein trafficking plays an essential role in the three dimensional organization of the dendritic arbor and in the integrity of the synaptic components.

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Why is it important?

Electron microscopy is the most efficient method for observation, morphological and morphometric study, and evaluation of the organelles of the neuronal perikaryon, dendritic profiles, spines, synapses, neuron-glial relationships, and morphology of the capillaries in the brain in normal and pathological conditions. The study in electron microscopy revealed dilatation of the cisternae of the smooth endoplasmic reticulum and substantial fragmentation of the cisternae of GA in numerous Purkinje cells of the cerebellar cortex. The cisternae of the GA were shorter in correlation to normal controls. Fragmentation of the cisternae of GA was also observed in granule cells in the vermis and the cerebellar hemispheres. It is worth emphasizing that the alterations of GA were also noticed in neurons without findings of tau pathology and in areas with minimal extracellular deposits of Aβ. The number of the vacuoles and vesicles, which are associated with the Golgi complex, was reduced in most Purkinje and granule cells of the cerebellum. Since vacuolization of the cell body was notnoticed in the majority of neurons, we may hypothesize that the alterations of the GA may occur quite independently from the cytoplasmic vacuolization. It has to be underlined that alterations of GA were also observed in the soma of astrocytes and in endothelial cells as well as in the pericytes of patients suffering from AD.

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