The Key to Early Alzheimer’s Detection

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Alzheimer’s disease is the most common cause of dementia and affects over 6 million Americans.1  It is important to research early indications of Alzheimer’s. This age-related, progressive disease is marked by the accumulation of protein aggregates in the brain (beta amyloid plaques around neurons and tau tangles within neurons) and by a decrease in brain glucose metabolism. Surprisingly, studies with subjects who were genetically predisposed to Alzheimer’s disease have found that those two neurological symptoms can begin to occur decades before Alzheimer’s symptoms become apparent. Currently, it is not possible to identify Alzheimer’s disease during this long preclinical period when interventions might be most effective.

Identifying biomarkers that may serve as early indicators of Alzheimer’s disease is an important subject of current Alzheimer’s research. The ideal identifying biomarker would be one that could be measured using inexpensive and noninvasive methods. To this end, Yao et al investigated in a recent paper whether mitochondrial dysfunction could be detected in extracellular vesicles (EVs) from the blood of Alzheimer’s patients. Given that EVs are small vesicles released into biological fluids like blood from many types of cells, they have been shown to contain analyzable components from the cells that release them such as nucleic acids and proteins.

Figure 1 from Yao et al. (2021) Mitochondrial electron transport chain protein abnormalities detected in plasma extracellular vesicles in Alzheimer’s Disease. The Azure Biomolecular Imager was used to image chemiluminescent blots analyzing markers present in the extracellular vesicle prep (panel B). Licensed under CC BY 4.0.

The authors collected EVs from the plasma of patients with high-probability early Alzheimer’s disease and from control patients with no evidence of dementia. A neuronal marker was used to selectively enrich for EVs from neuronal cells. The resulting EVs were characterized by Western blot to demonstrate that they contained EV markers and not markers associated with potential contaminants. To maximize image clarity and ensure accuracy, the chemiluminescent Western blots were imaged using the Azure Sapphire Biomolecular Imager.

Biochemical assays revealed that neuronally derived EVs from patients with Alzheimer’s disease had significantly lower levels of mitochondrial electron transport chain (ETC) complexes and lower levels of superoxide dismutase than EVs from control patients. In addition, the EVs from Alzheimer’s patients had significantly reduced activity of ETC complexes IV and V. The authors concluded that the neuron-derived EVs demonstrate the same abnormalities observed in Alzheimer’s tissues and model systems of Alzheimer’s disease and therefore may provide a biomarker for detecting early mitochondrial dysfunction in Alzheimer’s disease.

In addition to chemiluminescence imaging, the Sapphire Biomolecular Imager provides densitometry, phosphor, multichannel fluorescence, near-infrared, and white light imaging of blots, gels, tissues, and more. Learn more about the Sapphire and how Azure can support your research by clicking here.

 

SOURCES

  1. Yao PJ, Eren E, Goetzl EJ, Kapogiannis D. Mitochondrial electron transport chain protein abnormalities detected in plasma extracellular vesicles in Alzheimer’s Disease. Biomedicines. 2021;9(11):1587.
  2. Alzheimer’s Association. 2021 Alzheimer’s Disease Facts and Figures. Alzheimers Dement 2021;17(3).
  3. Mustapic M, Eitan E, Werner JK, et al. Plasma extracellular vesicles enriched for neuronal origin: A potential window into brain pathologic processes. Front Neurosci. 2017;11:278.

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