Mitochondria Are Related to Synaptic Pathology in Alzheimer's Disease

What is it about?

Morphological alterations of mitochondria may play an important role in the pathogenesis of Alzheimer's disease, been associated with oxidative stress and Aβ-peptide-induced toxicity. We proceeded to estimation of mitochondria on electron micrographs of autopsy specimens of Alzheimer's disease. We found substantial morphological and morphometric changes of the mitochondria in the neurons of the hippocampus, the neocortex, the cerebellar cortex, the thalamus, the globus pallidus, the red nucleus, the locus coeruleus, and the climbing fibers. The alterations consisted of considerable changes of the cristae, accumulation of osmiophilic material, and modification of the shape and size. Mitochondrial alterations were prominent in neurons, which showed a depletion of dendritic spines and loss of dendritic branches. Mitochondrial alterations are not related with the accumulation of amyloid deposits, but are prominent whenever fragmentation of the Golgi apparatus exists. Morphometric analysis showed also that mitochondria are significantly reduced in neurons, which demonstrated synaptic pathology.

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Why is it important?

Mitochondrial pathology was seen in the majority of the dendritic spines in all of the specimens, which consisted of substantial change of shape and size, fragmentation of cristae, and accumulation of osmiophilic material in a considerable number of mitochondria. Many dendritic profiles contained mitochondria, which showed an impressive polymorphism in the arrangement of the cristae, which sometimes showed a concentric configuration or in other places they were arranged in a parallel way to the long axis of the organelle. Some dendrites of Purkinje cells and a substantial number of climbing fibres contained very large elongated mitochondria. Small round mitochondria intermixed with dense bodies or associated with fragmentation of the Golgi apparatus were seen in the soma of a considerable number of neurons of the visual cortex, the hippocampus, the locus coeruleus, the red nucleus, the large polyhedral neurons of globus pallidus, and the Purkinje cells of the cerebellar cortex in contrast to normal control brains, in which the mitochondria looked unremarkable.

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