Mitochondria and synapses in Alzheimer's disease

What is it about?

Many morphological alterations of AD could be well linked to mitochondria changes, since blockage of mitochondrial energy production shifts APP metabolism to the production of more amyloidogenic forms of amyloid. In addition amyloid beta peptide promotes permeability transition pore in brain mitochondria.Recent studies reported increased mitochondrial fission and decreased fusion, due to increased amyloid beta (Aβ) interaction with the mitochondrial fission protein Drp 1, inducing increased mitochondrial fragmentation, impaired axonal transport of mitochondria and synaptic degeneration in AD.Decrease in energy metabolism and altered cytochrome c oxidase (CytOX) activity are among the earliest detectable defects in AD.Mitochondrial pathology was demonstrated in the majority of the dendritic spines in all of the studied specimens in AD. That consisted of substantial change of mitochondrial shape and size, fragmentation of cristae, and accumulation of osmiophilic material in a considerable number of mitochon‐ drial profiles. It is important to underline that mitochondrial pathology and fragmentation of the Golgi apparatus were seen in neurons which did not showed any tau pathology, such as accumulation of intracellular NFTs, and were located in areas with minimal deposits of Aβ peptide. However the the fragmentation of Golgi apparatus coexisted with mitochondrial alterations and dendritic and spinal pathology in the large majority of neurons.The size of the Golgi apparatus may be an index of neuronal activity. The fragmentation of the cisternae of Golgi apparatus may be associated with impaired trafficking of proteins to synapses and dendritic spines resulting in synaptic degeneration and cognitive impairment eventually.

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Why is it important?

Among the ongoing therapeutic efforts, those targeting basic mitochondrial processes, such as energy metabolism, free-radical generation, or specific interactions of disease-related proteins with mitochondria, hold great promise. On the basis of the mitochondrial pathology, in the pathogenetic spectrum in AD, new strategies inducing protection to mitochondria by the administration of efficient antioxidant factors could be introduced in the treatment of early cases of AD.

Perspectives