Treating Alzheimer’s: 6 Exciting Areas on the Cutting-Edge of Alzheimer’s Research

What Does the Future Hold for Alzheimer's Patients?   Photo by Andrea Piacquadio from Pexels
What Does the Future Hold for Alzheimer’s Patients? Photo by Andrea Piacquadio from Pexels

There are few things more devastating than Alzheimer’s disease. This brain disorder—which slowly destroys a person’s ability to remember even the most important details or think critically about even the most mundane task—progressively, irreversibly, and invisibly renders the person unable to lead a normal life, leaving them afraid, frustrated, and confused.

For the friends, family, and loved ones close to someone with Alzheimer’s disease, watching in slow motion as the spark, which once shone so brightly, begins to fade away as the disease progresses, is at the same time terrifying and frustrating.

For a disease which is almost invisible, often waved off in the early stages as simply ‘signs of age,’ Alzheimer’s is a significant issue for the health and wellbeing of senior citizens—and if demographic trends continue, will become an increasingly severe issue for our health systems and societies as a whole in the coming years.

How does Alzheimer’s Affect the Brain?

How does Alzheimer's Disease Affect the Brain?  Photo by Robina Weermeijer on Unsplash
How does Alzheimer’s Disease Affect the Brain? Photo by Robina Weermeijer on Unsplash

The human brain is one of the most complex systems we have ever encountered. A healthy human brain can have tens of billions of neurons—special cells that use electrical and chemical signals to transmit and process information—which are wired together in an inconceivably complex network of connections, creating the many structures within the brain.

Alzheimer’s disease is a brain disorder which damages brain cells and disrupts the brain’s ability to communicate across the neurons and brain structures, resulting in a loss in cognitive abilities such as memory.

Several unique changes can be observed in the brain, which are characteristic of Alzheimer’s disease. However, it is not entirely understood which of these changes are causing the disease and which are a result of its progression.

Amyloid Plaques

Dr. Alzheimer himself discovered one of the first changes in the brain to be associated with this disease. While studying the brain of a deceased woman who had been experiencing symptoms—with no identifiable origin—before her death, such as memory loss and problems with language, Dr. Alzheimer discovered that her brain was full of abnormal clumps of proteins.

These clumps of proteins, which are known as amyloid plaques and are still considered to be one of the hallmark characteristics of this disease, form when beta-amyloid proteins—which occur naturally in the brain—are present in abnormally high quantities and collect between neurons, disrupting communication and other cell functions.              

Neurofibrillary Tangle

In addition to uncovering amyloid plaques in his observation of the affected brain tissues, Dr. Alzheimer also encountered abnormal masses of tangled neurons—the result of accumulations of a protein known as tau.

In a healthy brain, tau helps to bind and stabilize the microtubules which transport nutrients and other molecules along the neurons. In the brain of a person with Alzheimer’s disease, the tau molecules become detached from the microtubule and instead join with other tau molecules, forming a tangled mess and disrupting the neurons’ ability to transport necessary chemicals.

Chronic Inflammation

More recently, developments in the study of how Alzheimer’s disease affects the structure of the brain have shown that the disease often leads to chronic inflammation of the brain.

Normally, cells known as glial cells, and especially microglia, are responsible for clearing waste and toxins from the brain. In the brain of a person with Alzheimer’s disease, these glial cells no longer clear waste, debris, and proteins, which leads to inflammation.

Cellular Death and Breakdown of Connections

With the buildup of amyloid plaques, the breakdown of microtubule structures resulting in the tangles of tau molecules, and the malfunction of the waste-removal systems, which lead to inflammation, the brain becomes much less hospitable to the survival of the neurons in the brain.

As the disease progresses, more and more neurons become injured and die off. This loss of neurons leads to the breakdown of neural connections, leading to a vicious cycle of cell damage and brain atrophy.

Current Treatment Options for Alzheimer’s

For the estimated 5.5 million Americans aged 65 and over who are known to be living with Alzheimer’s, the current outlook is not great.

This disease, whose symptoms typically don’t emerge until a person is in their mid-60s, is ranked as the sixth leading cause of death in the United States, though some estimates place it as high as number three.

One of the issues that makes Alzheimer’s disease so confounding is the fact that even now, there is still no single method for definitive testing for whether a patient has the disease, or how far the disease has progressed, while they are still alive. A medical diagnosis relies on a variety of tests and assessments to determine risk factors and to rule out other potential disorders that could be causing symptoms similar to those of Alzheimer’s. Though researchers are making progress in using medical imaging such as MRI and CT scans for the detection and monitoring of Alzheimer’s, there is still a lot of work to be done.

By the time a person is diagnosed with Alzheimer’s, the typical life expectancy is between three and ten years, depending on the age at which the diagnosis was made. And, although there are treatment options which can help manage symptoms and increase the quality of life somewhat in the years that remain, there is currently no cure for this disease.

Therapy & Counseling

For patients with mild to moderate Alzheimer’s disease, therapy, counseling, and other non-drug treatments are available to help with managing some of the behavioral symptoms associated with the disease itself or with the loss of memory and cognitive functioning that result from it.

Apart from memory loss, some of the most common symptoms and behavioral changes related to Alzheimer’s include:

Often the therapies and counseling will focus on planning ways to allow the patient to maintain as much independence as possible by creating routines and removing those things that may lead to confusion or frustration.

Medication

Though there are some non-drug treatment options that can help improve the standard of living of someone with Alzheimer’s, the main treatment options are pharmacological in nature. There are currently two classes of drugs approved by the FDA for use in the United States.

The first class are known as cholinesterase inhibitors and are approved for use in mild to moderate cases. These drugs act by boosting levels of acetylcholine, a chemical that is believed to be essential for normal functioning of memory and thinking ability. There are currently three different drugs in this class approved for use.

The second class of Alzheimer’s drugs, known as N-methyl D-aspartate (NMDA) antagonists, is approved for use with moderate to severe Alzheimer’s, and can be used alone or in conjunction with a cholinesterase inhibitor. This class of drugs is used to decrease symptoms associated with advanced Alzheimer’s, giving the patient extra months or years of independence. Currently, only one drug in this class is approved for use in the United States.

Research on Future Treatment Options Is Already Happening Around the World

Though current treatment for Alzheimer’s is limited and mainly focused on managing the symptoms and maintaining some form of independence and quality of life for as long as possible, they are, in essence, merely holding back the inevitable.

But for the doctors and researchers around the world who study this brain disease, that just isn’t good enough. Pharmaceutical companies, medical facilities, and research institutions across the globe are looking for the next generation of treatment options for Alzheimer’s. The hope is that they can unlock new ways of stopping the disease in its tracks, and ultimately preventing it from ever taking hold.

We are on the cusp of unlocking new treatment options as scientists look beyond merely treating the symptoms and on towards uncovering the secrets of treating the underlying processes and causes of the disease.

Targeting Beta-amyloid Plaques

Some of the current research strategies are taking aim at the beta-amyloid plaques which build up in the brain. Though many of these are still in the early stages, several have shown great promise.

One of the new types of drugs currently in the preclinical trial stage is a group of medications known as monoclonal antibodies. Researchers believe these drugs work by preventing beta-amyloid from clumping together and may even help to reduce the plaques which have already formed.

Another exciting development in this area involves another protein, known as Fyn, and how it interacts with beta-amyloid in the brain. When these two proteins combine, Fyn is over-activated, leading to damage in the connections between nerve cells. Testing in mice has found that certain drugs which act to inhibit Fyn resulted in increased activity in the brain and improved memory in some instances.

Untangling the Web of Tau

The Tau proteins, which usually are responsible for maintaining the structure of neurons, can collapse in the brain of a person with Alzheimer’s disease and become twisted into tangles of proteins that can damage the structure of the neurons and eventually destroy the neurons entirely.

There are currently research studies testing new drug treatments which stimulate the body’s own immune system to attack the abnormal Tau formations. Initial results in clinical trials have shown great potential, with up to 98.2% of participants developing antibodies to Tau proteins. The trials also showed positive results in potentially slowing the progression of the disease.

Fighting Inflammation

The brain inflammation caused by the abnormal behavior of microglial cells in the presence of beta-amyloid plaques and tau tangles can damage nearby neurons and lead to brain atrophy.

Several studies are currently underway to find ways to fight this inflammation either by activating other parts of the immune system to clear the toxins and debris or to reprogram the microglia cells so they no longer interact negatively with beta-amyloid or tau proteins.

In addition, researchers are studying a gene known as TREM2, which tells the microglia to clear beta-amyloid plaques. When this gene is not functioning correctly, microglia and other glial cells gravitate to the location they were supposed to clear of protein but fail to complete the cleanup process.

Where Do We Go from Here? The Future of Alzheimer’s Research

Though Alzheimer’s disease is a complex and devastating disorder that we still do not fully understand, the scientific and medical communities seem to be on the verge of unlocking some of the secrets to what causes this terrible brain disorder.

Research and clinical trials continue to search for new ways to understand how Alzheimer’s disease affects the brain and how the unique changes to the brain, which are so characteristic of the disorder, develop and interact with one another.

Looking even further into the future, beyond simply mitigating symptoms or holding back the progression of the disease, doctors and researchers are beginning to ask themselves if maybe it’s even possible to prevent the disease entirely,

Investigating the Link Between the Heart and the Brain

It is quite rare that a person with Alzheimer’s doesn’t also suffer from some form of cardiovascular issues as well. A variety of factors intermingle to create complex relationships between Alzheimer’s disease and deteriorating cardiovascular health that seem to show that these health issues are at once both cause and consequence of one another.

Researchers are looking to understand this head-heart connection and create new treatment options for future trials.

Alzheimer’s Prevention Trials

As with any disease, the ultimate goal for doctors and researchers is prevention. This is no different for Alzheimer’s. Though the majority of research and clinical trials as of yet have been focused on managing, mitigating, and delating the symptoms of the disease, there has been some promising movement on the prevention front.

Two such studies, the Autosomal Dominant Alzheimer’s Disease (ADAD) trial and the Generation Study form what is known as the Alzheimer’s Prevention Initiative (API). The studies in the API test therapies in people who have risk factors for Alzheimer’s, including genetic predisposition, but who have not yet developed symptoms.

These trials are looking for treatments that can delay or ultimately prevent the onset of Alzheimer’s entirely.

Increased Collaboration for Faster Treatment Development

In a show of unity and a sign of hope for families who have been touched by the pain that is Alzheimer’s disease, several major pharmaceutical companies, nonprofit foundations, and government advisors have come together to create a research alliance to help speed up the discovery and development of new treatments for Alzheimer’s. The partnership, a part of the Coalition Against Major Diseases (CAMD), is a trailblazing group initiative to share data from clinical trials regarding Alzheimer’s disease.

Researchers see this partnership as an encouraging step towards speeding up the development of new medications and making an often painstaking process much more effective and efficient.

There Is Hope for Better Treatment for Alzheimer's Patients.
There Is Hope for Better Treatment for Alzheimer’s Patients.