Alzheimer's Disease: The Powerhouse of the Cell

Many understand the basic function of mitochondria, an organelle that is the "powerhouse of the cell". Mitochondria generate energy through the creation of adenosine phosphate, ATP, and aid with sending signals between cells, as well as cell destruction.

When the neuronal pathways start to go awry in Alzheimer's Disease, mitochondrial dysfunction plays a large role. Calcium homeostasis is also central to mitochondrial function. As people age, neuroscientists predict that calcium pumps become less efficient, increasing the calcium levels seen in AD. Recent researchers have attempted to develop targets for Alzheimer's disease to regulate calcium receptors, reversing neurological changes.2 The mitochondrial calcium uniporter (MCU) allows calcium to enter the mitochondria due to increasing calcium levels, and can later be released through the mitochondrial permeability transition pore (mPTP).

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The Aβ plaques prevalent in AD can also disrupt calcium homeostasis. However, mitochondrial dysfunction usually precedes the formation of Aβ plaques, and is linked to the formation of Aβ. Since mitochondria are at the end of the electron transport chain, the production of ATP, needed for energy, can be decreased. At the same time, reactive oxygen species (ROS) can increase, leading to oxidative stress.

The reactive oxygen species often can lead to significant inflammation in nerve cells, and the larger central nervous system (CNS). This mechanism is primarily through oxidative stress, leading to DNA damage.

Recent developments have shown that ROS can influence neural differentiation, the process of stem cells differentiating into neurons, astrocytes, and oligodendrocytes. Because scientists now understand that neurogenesis occurs in the adult brain, Alzheimer's and other neurodegenerative diseases are affected.

References

1. D’alessandro, M. C. B., Kanaan, S., Geller, M., Praticò, D., & Daher, J. P. L. (2025). Mitochondrial dysfunction in Alzheimer’s disease. Ageing Research Reviews, 102713.

2. Ge M, Zhang J, Chen S, Huang Y, Chen W, He L, Zhang Y. Role of Calcium Homeostasis in Alzheimer's Disease. Neuropsychiatr Dis Treat. 2022 Mar 3;18:487-498. doi: 10.2147/NDT.S350939. PMID: 35264851; PMCID: PMC8901263.