What Is the Main Idea?

Alzheimer’s disease is the most common cause of dementia among older adults, and the incidence is increasing. In the free access research article “Comprehensive Bibliometric Analysis of Stem Cell Research in Alzheimer’s Disease from 2004 to 2022”, published in the journal Dementia and Geriatric Cognitive Disorders, the authors discuss the results of their review of research literature published about stem cells and Alzheimer’s disease over the last 20 years and highlight future research directions.

What Else Can You Learn?

In this blog post, Alzheimer’s disease is discussed. Stem cells and the specialization of cells to enable them to play different roles in the body are also described.

What Is Alzheimer’s Disease?

Alzheimer’s disease is a type of dementia. Dementia is an umbrella term that is used to describe a group of conditions that affect the nervous system (known as “neurological” conditions). They directly affect the brain and get worse over time (conditions like this are described as “progressive”), usually over a number of years.

Although symptoms can be similar among different types of dementia, and some people have more than one form, Alzheimer’s is associated with memory loss and confusion in the early stages. Mild symptoms and signs range from wandering, getting lost, and repeating questions to changes in mood or personality. More moderate symptoms include impulsive behavior, misplacing things, and problems recognizing family and friends, with people potentially losing the ability to communicate if the condition becomes severe.

Alzheimer’s disease is the most common type of dementia in adults and is usually diagnosed in people aged 60 years and older. It can develop in younger people but this is rare. Incidence is increasing and it is estimated that the number of people with Alzheimer’s disease worldwide will treble by 2050.

What Causes Alzheimer’s Disease?

Our understanding of the sequence of events that lead to the development of Alzheimer’s disease is still limited. It is well known that the brains of people with Alzheimer’s disease have abnormal clumps of proteins called “amyloid plaques” and tangled bundles of fibers called “tau tangles”. These are found throughout their brains, but rather than simply being caused by a build-up of plaques and tangles, Alzheimer’s disease is now believed to be a complex condition caused by a variety of factors – including genetic, environmental, and lifestyle factors – that affect the brain over time.

As well as having plaques and tangles, neurons (brain cells that transmit messages from one part of the brain to another) in people with Alzheimer’s disease become damaged and lose their connections with each other, and many other complex brain changes are thought to be involved. There is currently no cure for Alzheimer’s disease and treatment focuses on helping people maintain their brain health, slowing or delaying symptoms, and managing behavioral changes. There is growing evidence that adopting healthy lifestyle habits, like exercising regularly and eating a healthy diet, can reduce the risk of developing dementia, in addition to reducing the risk of other conditions like cancer and heart disease.

How Might Stem Cell-Based Therapy Help?

Cell differentiation is the process by which “immature” undifferentiated (unspecialized) cells take on specific characteristics and become specialized to have a particular role in the body. Stem cells are unique in that they can self-renew, are either undifferentiated or only partially differentiated, and are the source of specialized cell types, like red blood cells and types of brain cell.

Stem cells have become a focus of medical research because it is hoped that studying differentiation will give new insights into how some conditions develop. It is also possible to guide stem cells to become a particular cell type, raising the possibility that tissues that are damaged or affected by a disease could be regenerated or repaired (this is known as “regenerative medicine”).

Focuses of research regarding Alzheimer’s disease include:

  • attempting to replace injured or lost neurons,
  • increasing the production of chemicals in the brain that influence the growth of nervous tissue,
  • reducing the build-up of the proteins that form amyloid plaques and tau tangles,
  • increasing synaptic connections,
  • decreasing inflammation in the brain,
  • repairing metabolic systems that have gone wrong (metabolism is the process by which the body produces energy), and
  • improving the immediate environments of areas in the brain.

What Did This Study Investigate?

The authors of this study used an approach called “bibliometrics” to assess trends and developments across 3,428 stem cell research reports regarding Alzheimer’s disease published between 2004 and 2022. Bibliometrics uses mathematical and statistical methods to analyze and provide an overview of a large number of documents in a particular research field. It can help researchers understand the direction in which research in a given area is heading and can contribute to the formation of clinical guidelines. It can also identify where more collaboration between different research areas is needed and identify new avenues for study.

Their analysis showed that the number of reports published on stem cell research in Alzheimer’s disease has increased dramatically over the last 20 years, particularly since 2016. The increase since 2016 is partly attributed to the combination of induced pluripotent stem cell(iPSC)-based and 3D bioprinting techniques. iPSCs are cells that are derived by reprogramming differentiated skin or blood cells back into an embryonic-like “pluripotent” state (meaning that they can develop into many different cell or tissue types, just like the stem cells in a developing embryo).

This means that a person’s blood cells could potentially be treated to become iPSCs that could then produce new neurons. 3D bioprinting is a technology that uses living cells mixed with bioinks to print natural, 3D tissue-like structures. The combination of iPSC-based and 3D bioprinting techniques has meant that it has been possible to create cultures of cell that more closely mimic the situation in the brain.

Research Hot Spots and Future Directions

A number of fields have been key areas of research for some time. These include iPSCs, microglia, and mesenchymal stem cells. Mesenchymal stem cells are a type of stem cell that are unable to differentiate into blood cells and have limited self-renewal capacity. Microglia are specialized brain cells that regulate brain development, the repair of injury, and the maintenance of neural networks. There is significant interest in their roles in healthy brains and how their dysregulation may be involved in the development of neurological conditions.

Newer areas of research interest include the roles of mitochondrial dysregulation (mitochondria are the parts of the cell where energy is produced) and autophagy (a process by which old and damaged proteins or parts of cells are broken down and destroyed) in the development of Alzheimer’s disease.

Another research area is that of exosomes, tiny sac-like structures that are involved in cell-to-cell communication. Exosomes bud off the outer surfaces of cells and are found in body fluids including blood, saliva, and cerebrospinal fluid (the fluid found in the tissue that surrounds the brain and spinal cord). They carry DNA, RNA, and proteins from the cells from which they originate. Exosomes derived from a patient’s stem cells have a strong safety profile and are unlikely to provoke a strong immune reaction.

In addition, because their primary function is shuttling cargoes between cells, it is hoped that they may be used for patient-specific drug delivery in the future, which may prove to be a more successful approach than stem cell transplantation. Combined, these research directions raise the exciting possibility that the development of effective therapies for Alzheimer’s disease may not be far away.

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