Biosensors for Alzheimer’s

Are Electrochemical Biosensors the Future of Alzheimer’s Disease Diagnosis?

By SunJae Lee

About the Author

SunJae (Sunny) Lee is a senior at the International School of Beijing. She is fascinated by chemistry and biology (particularly Alzheimer’s disease) and genuinely passionate about service and giving back to the local community. In the future, she hopes to pursue a career in which she can combine these two interests.

Introduction

You most likely know someone that had been affected by the ever-terrifying Alzheimer’s disease. Maybe not a near family member or friend, but perhaps one of the following people: former US president Ronald Reagan, civil rights activist Rosa Parks, and author E.B. White [1]. All of these heroes, from the political or literature world, were affected by Alzheimer’s disease that led to the end of their careers.

Alzheimer’s disease is an irreversible neurodegenerative disease that “is predicted to affect 1 in 85 people globally by 2050” [2]. This disease is believed to be caused by a wide range of different factors, including old age, family history, genetic mutation, and head injury [3]. However, to this date researchers are still investigating the disease, as the exact reason for developing it is unknown. Once affected, Alzheimer’s disease aggravates at an alarming rate that leads to not only memory loss and cognitive impairments, but also several psychological impacts such as depression, stress, and anxiety [4]. The most threatening fact of all is that there is not yet an available cure or a reliable method of timely and accurate diagnosis [4].

To diagnose Alzheimer’s disease in a patient, doctors often examine their blood or urine samples for biomarkers that indicate presence of the disease. The main issue with this, however, is that bodily fluids have low concentrations of biomarkers that can be detected via traditional assays. The traditional assay method of enzyme-linked immunosorbent assay (ELISA), as well as magnetic resonance imaging (MRI) and positron emission tomography (PET) scan, have several disadvantages: time-consuming procedures, potential hazards to health, expensive instruments and need of highly trained professionals [5]. Though certain drugs have been demonstrated to slow down the progression of Alzheimer’s disease, it is usually too late by that point due to the difficulty of diagnosis at an early stage [6]. Hence, it is crucial to develop a simple, safe, and accurate method to diagnose Alzheimer’s disease, especially in the early stages of the disease. The new technology of biosensors, particularly electrochemical biosensors which is the focus of this article, present a desirable solution to the issues above and may be the future of early Alzheimer’s disease diagnosis.

 

What are Biosensors?

A biosensor is an analytical device that converts a biochemical signal into a quantifiable signal in the form of a current, light, or frequency [5]. Though there are various types, most biosensors integrate these three essential components: a bioreceptor, transducer, and signal output [5]. The bioreceptor utilizes biomolecules such as enzymes, lipids, antibodies, to bind to analytes of interest, which, in this case, would be proteins responsible for Alzheimer’s disease. A signal is created during this interaction, which the transducer then transforms into measurable data [7].

Why a biosensor would be a useful tool for diagnosis of Alzheimer’s disease

Scientists have found over the years that aggregation of the biomarkers amyloid-beta (Aβ) peptide and tau protein in the brain are responsible for the onset and progression of Alzheimer’s disease. However, with its complicated structure, they require highly sensitive and selective detection methods – biosensors satisfy precisely that [4]. The nature of biosensors allows for high sensitivity, easy fabrication, and effective miniaturization, which make them especially suitable for biomarker detection [4]. In the case of biosensors integrated with nanomaterials, its high surface area to volume ratio allows their electrical properties to be more susceptible to external influences. These biosensors can also efficiently interact with its target biomolecules that are comparable in size, resulting in higher sensitivity and accuracy of measurements [8].

Special features of electrochemical biosensors

The general process by which electrochemical biosensors operate is similar to that of the standard biosensor. However, electrochemical biosensors are unique in that they can produce an electrical signal proportional to the concentration of an analyte of interest [9]. This is done by measuring the electrical response generated as the reaction occurs between an analyte and the surface of the working electrode of the biosensor [5]. This feature is crucial in monitoring levels of bodily substances like glucose and may be especially useful in tracking concentrations of Alzheimer’s-linked amyloid-beta (Aβ) peptide and tau protein [9].

Electrochemical techniques are widely used because it allows for convenient, miniaturized, and portable devices to be made. To further increase sensitivity (more specifically, electrode response magnitude), scientists frequently apply methods to increase the electrode surface, incorporate more conductive material onto the coating of the electrode, or catalyze the reaction. Likewise, the selectivity of the biosensor can be increased by attaching antibodies that target specific biomolecules onto the electrode surface. [5]

Application of electrochemical biosensors in biomarker detection was found to be successful with cortisol, a biomarker of psychological stress [8]. When a nanosized electrode was integrated with nanosized sensing material and a miniaturized transducer, the electrochemical biosensor was shown to be capable of detecting cortisol at pg/mL levels within just 40 minutes [8]. This is faster than the MRI or PET scan, which can take up to 90 minutes, and certainly more efficient than the ELISA test, which can take days, even weeks, and sometimes lead to no result [11, 12, 13].

A similar process could be used to develop a biosensor capable of detecting amyloid-beta (Aβ) peptide and tau protein. Researchers have already begun to create a biosensor that incorporates nucleic acid aptamer bioreceptors, which are single-stranded DNA or RNA oligonucleotides [14]. This technology is attractive for biomarker detection because aptamers are incredibly versatile, hence capable of binding with a variety of biomolecules with high affinity and specificity [14, 15]. Though still in its developmental stages, such biosensor can soon potentially enable doctors to do quick screening and monitoring of Alzheimer’s disease in patients [8]. This could even allow them to diagnose the disease at an earlier stage and move onto treatments aimed to slow progression.

 

Challenges

Electrochemical biosensors demonstrate an ideal solution for early diagnosis of Alzheimer’s disease. However, for this technology to enter industries and begin commercialization and production at a large scale, it still has a long way to go. Costly materials, potential risks of operating at the nanoscale, and difficulty of storage are among the many factors scientists must consider before bringing them to be manufactured and used in real life [5].

Another step that must be taken before releasing electrochemical biosensors to actual hospitals is validating its effectiveness through multiple clinical trials. Though the design and idea behind using electrochemical biosensors in Alzheimer’s detection seem promising, this research is still at laboratory stages, and the method cannot officially be carried out until it has been ensured to work entirely [5].

Conclusion

To summarize, electrochemical biosensors function by producing an electrical signal proportionate to the concentration of an analyte of interest, thereby providing an excellent feature for monitoring levels of specific substances within the body. This particular type of biosensor is especially sensitive and selective due to its conductive and mechanical properties and thus is suitable for amyloid-beta (Aβ) peptide and tau protein detection. Although this technology is not yet polished and readily available, further research is expected to lead to a successful “Alzheimer’s sensor” that can be used clinically. Based on current progress, it is safe to anticipate a bright future for the involvement of electrochemical biosensors in early diagnosis of Alzheimer’s disease [5].

Discussion & Speculation

In the future, Alzheimer’s disease will become increasingly widespread, with the elderly population (age 65 or over) expected to grow from 8.5% to 17% of the world’s population by the year 2050 [16]. The likelihood of developing Alzheimer’s disease doubles every 5 years after the age of 65, meaning every elder who reaches this age may begin to worry about losing precious memories of their families and friends [3]. All of this stress and worry can be eliminated if we can find a way to develop a biosensor that lasts a lifetime for in vitro use. Today, infants and children receive vaccinations to build protection from various diseases that could infect them in the future. In the same way, we should aim towards developing a long-lasting biosensor that we could insert into our body well before we reach the age at which we become susceptible to the disease. This way, we would know immediately if and when we start aggregating amyloid-beta (Aβ) peptide and tau protein for Alzheimer’s disease. Although this is not a proposal for an ultimate cure for Alzheimer’s disease, I believe finding a way to diagnose Alzheimer’s disease early is the first and vital step in tackling this disease.

Acknowledgments

I owe many thanks to my professor, Dr. Jagannath Padmanabhan from Stanford University, for providing me with the knowledge, as well as the inspiration and excellent opportunity to write this research article. Through the nanobiomaterials course that he designed, I was able to gain insights into a completely new aspect of biological sciences. Additionally, Dr. Padmanabhan’s enthusiastic, engaging, and ever-encouraging approach to teaching drove me to explore beyond the scope of the course and incorporate nanobiomaterials into a field that I am personally interested in.

References. 

1. Kennard, Christine. “Famous People with Alzheimer’s Disease and Other Types of Dementia.” Verywell Health, About, 19 Dec. 2017, www.verywellhealth.com/famous-people-with-alzheimers-98082. Accessed 23 Aug. 2018.
2. Li, S.-S., Lin, C.-W., Wei, K.-C., Huang, C.-Y., Hsu, P.-H., Liu, H.-L., … Ma, C.-C. M. (2016). Non-invasive screening for early Alzheimer’s disease diagnosis by a sensitively immunomagnetic biosensor. Scientific Reports, 6, 25155. Retrieved from http://dx.doi.org/10.1038/srep25155
3. “Risk Factors.” Alzheimer’s Association, www.alz.org/alzheimers-dementia/what-is-alzheimers/risk-factors. Accessed 23 Aug. 2018.
4. Kaushik, A., Jayant, R. D., Tiwari, S., Vashist, A., & Nair, M. (2016). Nano-biosensors to detect beta-amyloid for Alzheimer’s disease management. Biosensors and Bioelectronics, 80, 273–287. https://doi.org/https://doi.org/10.1016/j.bios.2016.01.065
5. Pasinszki, Tibor, et al. Carbon Nanomaterial Based Biosensors for Non-Invasive Detection of Cancer and Disease Biomarkers for Clinical Diagnosis. National Center for Biotechnology Information, 20 Aug. 2017.
6. Rushworth, J. V, Ahmed, A., Griffiths, H. H., Pollock, N. M., Hooper, N. M., & Millner, P. A. (2014). A label-free electrical impedimetric biosensor for the specific detection of Alzheimer’s amyloid-beta oligomers. Biosensors and Bioelectronics, 56, 83–90. https://doi.org/https://doi.org/10.1016/j.bios.2013.12.036
7. Shukla, S. K., Govender, P. P., & Tiwari, A. (2016). Chapter Six – Polymeric Micellar Structures for Biosensor Technology. In A. Iglič, C. V Kulkarni, & M. B. T.-A. in B. and L. S.-A. Rappolt (Eds.) (Vol. 24, pp. 143–161). Academic Press. https://doi.org/https://doi.org/10.1016/bs.abl.2016.04.005
8. Grieshaber, Dorothee et al. “Electrochemical Biosensors – Sensor Principles and Architectures.” Sensors (Basel, Switzerland)3 (2008): 1400–1458. Print.
9. Hammond, Jules L. et al. “Electrochemical Biosensors and Nanobiosensors.” Ed. Pedro Estrela. Essays in Biochemistry1 (2016): 69–80. PMC. Web. 23 Aug. 2018.
10. Abdulbari, H. A., & Basheer, E. A. M. (2017). Electrochemical Biosensors: Electrode Development, Materials, Design, and Fabrication. ChemBioEng Reviews, 4(2), 92–105. https://doi.org/10.1002/cben.201600009
11. Davis, Charles Patrick. “ELISA Tests.” Edited by John P. Cunha. MedicineNet, www.medicinenet.com/elisa_tests/article.htm.
12. “How It’s Performed.” NHS, 10 July 2015, www.nhs.uk/conditions/mri-scan/what-happens/. Accessed 23 Aug. 2018.
13. “PET Scan: Test Details.” Cleveland Clinic, my.clevelandclinic.org/health/diagnostics/10123-pet-scan/test-details.
14. Shui, D. Tao, A. Florea, J. Cheng, Q. Zhao, Y. Gu, W. Li, N. JaffrezicRenault, Y. Mei, Z. Guo, Biosensors for Alzheimer’s disease biomarker detection: A review, Biochimie (2018), doi: 10.1016/j.biochi.2017.12.015
15. “What Is an Aptamer? – Aptamers and SELEX.” Base Pair Biotechnologies, www.basepairbio.com/what-is-an-aptamer/. Accessed 24 Aug. 2018.
16. “World’s Older Population Grows Dramatically.” National Institutes of Health, 28 Mar. 2016, www.nih.gov/news-events/news-releases/worlds-older-population-grows-dramatically.