Diseases and Disorders

Alzheimer's and Nanotechnology: The Missing Puzzle Piece

Akhil Kumar


Introduction

Alzheimer’s is a disease that affects over 44 million people worldwide. To many families, when a loved one receives a diagnosis of Alzheimer's, it may seem like the end of the world. They have to endure their loved ones losing precious memories and forgetting who they actually are. Recently, scientists and researchers have discovered a new way to tackle this problem. Nanotechnology is a new kind of science that allows researchers to study extremely small particles which can help them develop a cure or can lead them to make an early diagnosis. This entry will talk about the new therapies being developed and how it all fits into the bigger picture.

 

The Formation of Alzheimer's Disease
Gold nanoparticles helping visualize the beta-amyloid proteins.

In healthy aging, the brain shrinks but does not lose a lot of neurons. In Alzheimer’s disease, many neurons stop functioning, lose connections with other neurons, and eventually die. The disease disrupts vital processes to neurons and their networks which results in the loss of memory, communication, logical reasoning, and social behavior. A person with Alzheimer’s gradually loses their ability to function independently and ultimately dies from the disease. 

A lot of the molecular and cellular changes that happen in a person who has Alzheimer’s occur long before the first sign of memory loss (about 7-10 years). There are five main causes of this disease, and they are all interconnected in many different ways.

  1. Amyloid Plaques
    • The protein, beta-amyloid, is formed from the breakdown of a larger protein called the amyloid precursor.  Beta-amyloid may come in different molecular forms and one such form, beta-amyloid 42, is known to be extremely toxic. The protein is naturally found in the brains of humans but abnormal levels of this protein can lead to them clumping together to form plaques that form between neurons that disrupt cell function.
  1. Chronic Inflammation

    • Chronic inflammation is caused by the buildup of glial cells which are normally meant to help keep the brain free of any debris. In a healthy brain, microglia and astrocytes (types of glial cells) engulf and destroy waste and toxins. In Alzheimer’s, microglia fails to clear away the waste, debris, and the protein collections which include beta-amyloid plaques. A study found the TREM2 gene to be the culprit of the abnormal function of microglial cells. TREM2 usually tells the cells to clear the beta-amyloid plaques from the brain and it is supposed to help fight inflammation. In the people where this gene does not function normally, plaques build up between neurons and they collect around the neurons but fail to perform their tasks. When this happens, they also release chemicals that cause chronic inflammation and further damage the neurons which they are meant to protect.

  2. Vascular Contributions

    • The majority of people who have Alzheimer’s also have a lot of vascular issues such as beta-amyloid buildup in brain arteries, atherosclerosis (hardening of the arteries), and mini-strokes. These vascular problems lead to reduced blood flow and oxygen to the brain and to the breakdown of the blood-brain barrier which protects the brain from harmful agents and only allows necessary agents to enter, such as glucose. A faulty blood-brain barrier prevents glucose from reaching the brain and prevents it from clearing away the toxic beta-amyloid and tau proteins. This results in inflammation which further adds to the vascular problems in the brain. Alzheimer’s is the cause and the consequence of most of the vascular problems that occur in the brain.

  3. Loss of Neuronal Connections and Cell Death

    • As neurons are injured and die off, the connections between networks of neurons break down and many brain regions begin to shrink. This process is known as brain atrophy and by the final stages of Alzheimer’s this process is widespread which causes significant loss of brain volume and eventually results in death.

All of the causes of the disease are linked together, but the main cause of the disease in most people is the buildup of plaque in the brain. Some of the causes may or may not happen depending on the type of person and the severity of the disease. Alzheimer’s may also be caused by a variety of other reasons such as genetic mutations, age, gender, lifestyle, cognitive impairment, etc.  [1][2].

 

Nanotechnology and Nanoparticles Overview

Nanotechnology is the study of extremely small things and is used in all fields such as chemistry, biology, engineering, and many more. Nanotechnology involves the ability to see and control individual atoms and molecules [3]. Nanomaterials have a relatively large surface area when compared to a material that has the same mass but in a larger form. This is because as objects get smaller their surface area to volume ratio increases, which means that the rate at which the volume increases is not the same as the rate of decrease in the object’s surface area. When objects are this small, they exhibit more quantum effects and don’t follow normal physics laws. For example, Vantablack 2.0, is the most black paint in the world and absorbs almost all of the light that reaches it [4].

Nanoparticles are microscopic particles between the size of 1 nanometer to 100 nanometers, as defined by the International Organization for Standardization (ISO). Gold nanoparticles are a type of nanoparticle that has the ability to get extremely small, and usually have a diameter of 5nm or less. They can be used in many applications but are mainly used as a catalyst (a substance that increases the rate at which another substance goes through a chemical change without undergoing any permanent chemical change itself) to help reactions occur. Gold nanoparticles also have the capability to convert certain wavelengths of light into heat. This occurs because gold contains electrons that are free to move throughout the metal and these electrons help conduct a current through the gold when a voltage is applied to it. Depending on the size and shape of the nanoparticles, these free electrons absorb energy from particular wavelengths of light. If it absorbs the right wavelength, a cloud of free electrons will form on the surface of the gold nanoparticles thus generating heat [5].

 

Nanoparticles and Alzheimer's

To develop a treatment, researchers and scientists have to properly visualize the protein build up inside and around neurons. If we get to know more about their structure it could lead to the detection of weak spots that could be targeted for treatment. On March 11, 2020, scientists from EPFL published a solution. The research showed that gold nanoparticles with a diameter of about 3nm have the unique ability to label amyloid proteins in a hydrated state. It was done using a specialized form of TEM called cryogenic transmission electron microscopy (cryo-EM), in which they first rapidly freeze the proteins to a very low temperature and they then can be visualized in their original state without having to be stained or modified beforehand thus making the visualization of the amyloids a lot easier [6].

Another application for nanoparticles is that they could break up the beta-amyloid plaques in the brain. A research study published from the University of Michigan at Ann Arbor and South Korea’s Kyungpook National University showed that when a short chain of amyloid peptides wraps around a tetrahedron-shaped nanoparticle, the nanoparticles’ edges destroy the peptides which prevent the additional peptides from attaching to the chain. The scientists used CdTe nanoparticles for their particularly sharp-faced structures. The researchers think this work offers a blueprint for the nanoscale engineering of nanoparticles from a variety of materials with properties similar to the CdTe nanoparticles. The problem with CdTe nanoparticles is that they are toxic and can’t be used in vivo, which means they can’t be used in a living organism. This research is an excellent proof-of-concept that demonstrates that nanoparticles can be devolved to break up protein bonds in the brain which can lead to the eventual cure for Alzheimer’s [7].

 

Conclusion

To summarize, Alzheimer’s is caused by a variety of reasons, some of which many researchers still do not understand to this day. Nanoparticles give researchers hope that they can finally solve what seemed like an impossible puzzle. Even though it seems like a never-ending puzzle, we just have to find the right pieces to put together. Nanoparticles are just one piece of that puzzle and I hope that in the future we could uncover more pieces of this puzzle that could someday lead to the cure to this incurable disease.


References


  1. (16/05/2017). What Happens to the Brain in Alzheimer's Disease? National Institute on Aging. https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease. Retrieved: (01/04/2020).

  2. Story, M. Colleen. (08/12/2016). Causes of Alzheimer’s: Is It Hereditary? Healthline. https://www.healthline.com/health/alzheimers-hereditary. Retrieved: (01/04/2020).

  3. What is Nanotechnology? Nano.gov. https://www.nano.gov/nanotech-101/what/definition. Retrieved: (02/04/2020).

  4. What is nanotechnology? Nanowerk. https://www.nanowerk.com/nanotechnology/introduction/introduction_to_nanotechnology_1.php. Retrieved: (02/04/2020).

  5. Gold Nanoparticles. UnderstandingNano.com. https://www.understandingnano.com/gold-nanoparticles.html. Retrieved: (02/04/2020).

  6. (13/03/2020). Researchers Target Amyloid Fibrils With Gold Nanoparticles. Neuroscience News & Research. https://www.technologynetworks.com/neuroscience/news/researchers-target-amyloid-fibrils-with-gold-nanoparticles-332010. Retrieved: (02/04/2020).

  7. Greenemeier, Larry. (20/05/2011). Nanoparticles Enlisted to Impede Alzheimer's-Inducing Brain Plaque. Scientific American. https://www.scientificamerican.com/article/nanotechnology-protein-amyloid-alzheimers/. Retrieved: (02/04/2020).

Akhil Kumar

Akhil Kumar


I am an extremely motivated high school student who loves researching and learning more about neuroscience and the inner workings of the brain. I have developed many research projects relating to Alzheimer's, Nanotechnology, and Brain Computer Interfaces. You can connect with me through LinkedIn: www.linkedin.com/in/akhil-kumar28 and I look forward to all the great initiatives and events this organization has planned for youth!!