Tau Positive Neurons Show Marked Mitochondrial Loss and Nuclear Degradation in Alzheimer's Disease

Author(s): Melissa Wee, Fariba Chegini, John H.T. Power*, Shohreh Majd.

Journal Name: Current Alzheimer Research

Volume 15 , Issue 10 , 2018

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Abstract:

Background: Alzheimer's disease (AD) pathology consists of intraneuronal neurofibrillary tangles, made of hyperphosphorylated tau and extracellular accumulation of beta amyloid (Aβ) in Aβ plaques. There is an extensive debate as to which pathology initiates and is responsible for cellular loss in AD.

Methods: Using confocal and light microscopy, post mortem brains from control and AD cases, an antibody to SOD2 as a marker for mitochondria and an antibody to all forms of tau, we analyzed mitochondrial density in tau positive neurons along with nuclear degradation by calculating the raw integrative density.

Results: Our findings showed an extensive staining of aggregated tau in cell bodies, dystrophic neurites and neurofilaments in AD with minimal staining in control tissue, along with a marked decrease in mitochondria in tau positive (tau+) neurons. The control or tau negative (tau-) neurons in AD contained an even distribution of mitochondria, which was greatly diminished in tau+ neurons by 40%. There were no significant differences between control and tau- neurons in AD. Tau+ neurons showed marked nuclear degradation which appeared to progress with the extent of tau aggregation. The aggregated tau infiltrated and appeared to break the nuclear envelope with progressively more DNA exiting the nucleus and associating with the aggregated intracellular tau.

Conclusion: We report that the mitochondrial decrease is likely due to a decrease in the protein synthesis rather than a redistribution of mitochondria because of the decreased axonal transport. We suggest that the decrease in mitochondria and nuclear degradation are key mechanisms for the neuronal loss seen in AD.

Keywords: Mitochondrial loss, SOD2, tau phosphorylation, Alzheimer`s disease, nuclear degradation, decrease in protein synthesis.

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Article Details

VOLUME: 15
ISSUE: 10
Year: 2018
Page: [928 - 937]
Pages: 10
DOI: 10.2174/1567205015666180613115644
Price: $58

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