Did you know that every three seconds, someone in the world develops dementia [1]? With cases at more than 55 million worldwide, this figure is projected to skyrocket in the coming decades as the elderly population increases.

Dementia is a condition characterized by decreased brain functionality, resulting in debilitating symptoms that impact an individual’s livelihood. With no cure for dementia, the next best way to lessen its impact on an individual is by providing them early awareness of their condition [2]. This would provide more time for afflicted individuals to come to terms with their diagnosis and prepare for it – as opposed to gradually losing brain function and ending up in precarious conditions.

The potential to provide an early diagnosis lies in a biosensor developed by researchers at Gacheon University and the University of Danang, the fluorescent-based aptasensor. The technology is aimed at diagnosing the most common form of dementia, Alzheimer’s disease (AD)[3].

Aptasensors are based around aptamers, which are short DNA or RNA molecules that bind to a specific target [4]. Like a magnet, the aptamer will bind to its target when in the target’s in range. In this study, the aptamer used matches the RNA of p-tau231–a variant of p-tau which is one of the two major AD biomarkers. Biomarkers are biological indicators of a disease’s presence, and p-tau231 happens to be a highly specific AD indicator that does not appear in other forms of dementia [5].

The aptasensor uses three main components [3]. First, fluorescent light emitting particles called nitrogen-doped carbon dots (NCDs). NCDs are arranged on the base of the aptasensor, lighting it up like a flashlight. They are used because of their excellent biocompatibility and easy preparation methods. Second, a human serum. For example, a blood sample that potentially contains p-tau231. And lastly, matching aptamers.

How it works

Starting off, the intensity of light emitted by the NCDs is measured with multi-plate microplate readers, which capture fluorescent spectra. Then, the aptasensor works in two steps: fluorescent quenching and fluorescent recovery [3].

The process of fluorescent quenching begins, where the NCDs are blocked out as the aptamers are laid on top of them. The light intensity, now significantly less, is measured again.

Finally, fluorescent recovery occurs. The aptasensor is exposed to the blood sample and some aptamers bind to the p-tau231 present, lifting off of the NCDs to reveal light. The intensity of light emitted is measured again for the final time.

The intensity of light recorded before and after blood exposure can quantify how much p-tau231 was in the blood sample. The more light “recovered” during exposure, the more p-tau231 in the blood sample. Thus, this technology not only detects the biomarker’s presence but also how much there is in a sample, which could indicate AD severity.

The results of this study found that the fluorescent-based aptasensor has excellent sensitivity for detecting p-tau231. However, further research is needed in assessing its sensitivity to detecting other p-tau variants which could indicate other dementias. Additionally, there are a few implications of the study. Firstly, it has opened doors on a new technology that could potentially diagnose AD early. It could also address the issues of inaccessible diagnosis practices, especially financial cost. The current standard for AD diagnosis, a positron emission tomography (PET) scan, costs between $5,000 and $8,000 [6]. Should the aptasensor be approved for diagnosis, it would be more accessible financially as its primary components, aptamers and NCDs, are inexpensive to synthesize.

References

1. Barros, D., Borges-Machado, D., Ribeiro, O., Carlvalho, J. 2020. Dementia and COVID-19: the ones not to be forgotten. American Journal of Alzheimer’s Disease & Other Dementias, 35. 10.1177/1533317520947505
2. Alzheimer’s Association, “2022 Alzheimer’s Disease Facts and Figures,” Alzheimers Dement 2022,18 https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf
3. Phan LMT, Cho S, Cardoso S, Carvalho C, Catarina Correia S. 2022. Fluorescent aptasensor and colorimetric aptablot for p-tau231 detection: toward early diagnosis of Alzheimer’s disease. Biomedicines, 10(1):93. https://doi.org/10.3390/biomedicines10010093
4. Szeitner, Z., András, J., Gyurcsányi, R. E., Meszáros R. 2014. Is less more? Lessons from aptamer selection strategies. Journal of Pharmaceutical and Biomedical Analysis, 101(58-65). https://doi.org/10.1016/j.jpba.2014.04.018
5. NIH. 2022, Jan 21. How biomarker’s help diagnose dementia. Retrieved from https://www.nia.nih.gov/health/how-biomarkers-help-diagnose-dementia
6. Poslusny, C. How much does a PET scan cost? Retrieved from https://www.newchoicehealth.com/pet-scan/cost