Title:Tau Positive Neurons Show Marked Mitochondrial Loss and Nuclear Degradation in Alzheimer's Disease
VOLUME: 15 ISSUE: 10
Author(s):Melissa Wee, Fariba Chegini, John H.T. Power* and Shohreh Majd
Affiliation:Neuronal Injury and Repair Laboratory, College of Medicine and Public Health, Flinders University, Adelaide, Neuronal Injury and Repair Laboratory, College of Medicine and Public Health, Flinders University, Adelaide, Neuronal Injury and Repair Laboratory, College of Medicine and Public Health, Flinders University, Adelaide, Neuronal Injury and Repair Laboratory, College of Medicine and Public Health, Flinders University, Adelaide
Keywords:Mitochondrial loss, SOD2, tau phosphorylation, Alzheimer`s disease, nuclear degradation, decrease in protein
synthesis.
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.
