Mitochondrial alterations in Alzheimer's disease

What is it about?

Morphological alterations of mitochondria may be related to metabolic and energy deficiency in neurons in Alzheimer’s disease and other neurodegenerative disorders. Mitochondrial dysfunction is also a hallmark of Aβ peptide induced neuronal toxicity in Alzheimer’s disease. A general change in glucose utilization, increased oxidative stress, and Ca2+ deregulation are additional metabolic defects in the AD brain that may also be associated with defective mitochondrial function the result is a cycle of increased mitochondrial dysfunction causing increased oxidative damage until the cellular energy supply falls below the threshold for cellular survival. In a series of studies on the morphological and morphometric estimation of mitochondria in Alzheimer’s disease, by electron microscopy we noticed substantial morphological and morphometric changes in the neurons of the hippocampus, the acoustic cortex, the frontal cortex, the cerebellar cortex, the climbing fibers, the thalamus, the globus pallidus, the red nucleus and the locus coeruleus. The morphological alterations consisted of considerable changes of the mitochondrial cristae, accumulation of osmiophilic material, and decrease of their size, in comparison with the normal controls. Mitochondrial alterations were particularly prominent in neurons, which showed loss of dendritic spines and abbreviation of the dendritic arborization. The ultrastructural study of large number of neurons in the thalamus and the red nucleus revealed that the mitochondrial alterations did not coexist with cytoskeletal pathology and accumulation of amyloid deposits, though they were prominent in neurons, which demonstrated fragmentation of the cisternae of the Golgi apparatus. Morphometric analysis showed that mitochondria are significantly reduced in Alzheimer’s disease. The relationship between the site and extent of mitochondrial abnormalities and the synaptic alterations suggests an intimate and early association between these features in Alzheimer’s disease.

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Why is it important?

The mitochondria demonstrated a wide variation of size and shape in comparison with those of the normal control brains. The ultrastructural study of the cerebellar cortex, the climbing fibres, the thalamus, the globus pallidus, the red nucleus and the locus coeruleus revealed an impressive polymorphism of the mitochondria in the soma of the nerve cells as well as in the axonal and dendritic profiles of the majority of neurons. The majority of the mitochondria were small round or elongated. A substantial number of them showed disruption of the cristae, though others included osmiophilic material. Some dendritic profiles included mitochondria, which showed an impressive polymorphism in the arrangement of the cristae, which sometimes showed a concentric configuration or they were arranged in a parallel way to the long axis of the organelle . The polymorphismof the mitochondriawas particularly impressive in dendritic profiles of neurons of the locus coeruleus , where morphological alterations of the mitochondria coexisted with fragmentation of the Golgi apparatus . Small round mitochondria intermixed with dense bodies were seen in large number of neurons in globus pallidus Morphological alterations of the mitochondria were seen in the soma, the perivascular astrocytic processes and the astrocytic sheaths in Alzheimer’s brains in contrast to normal controls, where the mitochondria looked normal.From the morphometric point of view the ellipsoid mitochondria in normal controls appear to have an average diameter of 650 ± 250 nm and a mean axial ratio of 1.9 ± 0.2. The round or global mitochondria in normal controls appeared having a mean mitochondrial radius of 350 nm. In Alzheimer’s disease brains, the ellipsoid mitochondria of the neurons appear to have an average diameter of 510 ± 250 nm and a mean axial ratio of 1.7 ± 0.2. The round mitochondria have a mean radius of 280 nm. The morphological alteration of the mitochondria seen in subcortical centres, such as in the thalamus, the globus pallidus, the red nucleus and the locus coeruleus pleads in favour of a generalized mitochondrial dysfunction in Alzheimer’s disease, which may be associated with wide neuronal loss and synaptic alterations, seriously affecting, as a consequence, the mental faculties, which are basically related to extensive neural nets .

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