Mitochondrial alterations Alzheimer's disease

Abstract

Morphological alterations of mitochondria may be related to metabolic and energy deficiency in neurons in Alzheimer's disease (AD) and other neurodegenerative disorders. In previous studies on the morphological and morphometric estimation of mitochondria in AD electron microscopy revealed substantial morphological and morphometric changes in the hippocampus, the acoustic cortex, the frontal cortex, and the cerebellum. This study extends this observation to subcortical centers, namely the thalamus, the globus pallidus, the red nucleus, and the locus caeruleus in 10 brains of patients who suffered from AD. The morphological alterations consisted of very obvious 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 a 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. However, they were prominent in neurons, which demonstrated fragmentation of the cisternae of the Golgi apparatus. The morphological alterations of the mitochondria presumably suggest oxidative damage in neurons in AD brains.

The proteasomal system

“…Cytotoxic effects of b-amyloid are the result of many different factors. Among them a direct influence on the mitochondria, decreasing their amount in the mainly affected areas of AD-brains and changing their morphology (Baloyannis et al, 2004) in affected neurons. The cellular functions of the APP family are still unknown, but potentially APP may be involved in calcium homeostasis (Mattson et al, 1993;Milward et al, 1992), cell growth and adhesion (Rossjohn et al, 1999;Mattson, 1997), axional vesicle transport (Gunawardena et al, 2003) and regulations of free metal ions Adlard and Bush, 2006).…”

The vascular factor in Alzheimer's disease: A study in Golgi technique and electron microscopy

“…The intracellular accumulation of neurofibrillary tangles and the extracellular amyloid deposits defined as neuritic plaques are the main hallmarks of the disease [4,5], though the neurotoxicity and synaptotoxicity of oligomeric Aβ species causing neuronal loss and synaptic degeneration plot the final profile of the disease [6]. Although substantial progress has been made the last four decades in approaching the pathogenetic background of Alzheimer's disease, it remains still enigmatic [7], however, a growing amount of data exists, which pleads in favor of the possible implication of the dysfunction of mitochondria in neurodegenerative disorders, including AD [8][9][10]. In addition, a substantial body of evidence suggests that the vascular factor may play an essential role in plotting the pathogenetic background of AD [11,12], Although cerebrovascular amyloidosis, is a common finding in Alzheimer's brains [13], the structural deformities of the brain capillaries, may be a crucial factor, resulting in hypometabolism of brain areas related with mental activities [14].…”

Dendritic pathology in Alzheimer's disease

“…In our previous studies on Alzheimer's disease brains we have seen and described pathological alterations of mitochondria in the soma and the dendrites in a large number of neurons in subcortical centres, the cortex of the brain hemispheres and the cerebellum [1,2,33,36,37] associated with synaptic pathology.…”

“…In the neuronal dendrites of patients who suffered from Alzheimer's disease the number of the mitochondria was dramatically decreased in various areas of the cortex and the subcortical centres, in comparison with the normal controls, coinciding with the loss of dendritic branches and the tremendous loss of the dendritic spines [33].…”