Category Archives: Science Articles

Ultrasound and Microbubbles May Be Used to Treat Alzheimer’s Disease

Alzheimer’s disease, the most common form of dementia, is characterized by the buildup of toxic, sticky plaques inside the brain. These plaques are made of a protein called amyloid-beta. Although hundreds of drug candidates that try to remove amyloid-beta from the brain have been tested in clinical trials, these have been a resounding failure (see “Where’s our cure to Alzheimer’s disease?”). This has led scientists to try out new methods for treating the disease.

One of the most intriguing ideas for treating Alzheimer’s is to use ultrasound. Ultrasound uses high-frequency sound waves outside the range of human hearing. These sound waves can pass through soft tissues but bounce off of denser things such as bone, which is how ultrasound can generate the image of a fetus during pregnancy.

Ultrasound has many uses outside of imaging. One recent techniques involves injecting the patient with tiny “microbubbles.” When hit with an ultrasound pulse, the microbubbles expand and contract. This allows them to gently press against the blood vessel walls without damaging them.

The microbubble ultrasound technique has an interesting effect inside the blood-brain barrier (BBB). The BBB is a complex structure that surrounds blood vessels inside the brain. It prevents harmful toxins and pathogens from entering the brain, but can also make it difficult for waste products (including amyloid-beta) to be cleared away.

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The cells surrounding blood vessels in the brain, known as the blood-brain barrier, prevent large molecules from passing through. Image Source

When microbubbles inside the brain’s blood vessels expand, they can temporarily open the BBB. This not only allows for enhanced clearance of waste products, but also activates many immune pathway in the brain that further assist with this process.

Early experiments involving mice have been encouraging. In 2013, 2014, and 2015, three different research groups found that mice that were genetically engineered to develop Alzheimer’s disease showed improvements after ultrasound/microbubble treatments. This included reduced levels of amyloid-beta, improved spatial memory, and more newborn neurons inside the hippocampus, a part of the brain associated with memory.

Several human trials involving ultrasound are currently being planned or in progress. One small trial of five subjects found that the ultrasound device could safely and reversibly open the BBB. However, we still need to wait for more results to come out before we’ll know whether this strategy is effective for treating Alzheimer’s.

It also remains to be seen whether ultrasound may come with any unforeseen consequences. It’s possible that opening the BBB could allow certain immune cells or pathogens to enter the brain, creating an opportunity for autoimmune reactions or brain infections. Despite the potential risks, researchers remain hopeful that ultrasound could offer a noninvasive means for treating Alzheimer’s disease in the future.

 

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Why Are Women Twice as Likely to Get Alzheimer’s Disease?

Of the more than 5 million Americans living with Alzheimer’s disease, nearly 2/3 of them are women. A woman in her 60s has a 1 in 6 chance of later developing Alzheimer’s, compared to only 1 in 11 for a man. What is the cause for this sex imbalance?

A major player in this question is the APOE gene (see The Genetics of Alzheimer’s Disease for more detail). This gene comes in three different forms: APOE2, APOE3, and APOE4. Each of us inherits two copies of this gene (one from each parent). If you have one copy of APOE4, your risk of Alzheimer’s increases threefold, while having two copies of APOE4 increases your risk by fifteen times. For reasons that remain unclear, the APOE4 allele seems to be a stronger risk factor for women than men, which could help to explain the difference in Alzheimer’s prevalence.

Some lines of research suggest that sex hormones may also play a role. Specifically, reduced estrogen levels, which commonly occur during menopause, are associated with increased risk of Alzheimer’s. Several studies have shown that women with Alzheimer’s tend to have lower estrogen levels in their brains. Pregnancy also reduces lifetime exposure to estrogen, which may explain why women who have had biological children have a higher risk of dementia than women without biological children. Similarly, women who have had a hysterectomy or oophorectomy (removal of the uterus or ovaries), which can induce menopause at an earlier age, also have an increased risk of dementia.

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A woman’s estrogen levels decrease as they approach menopause, which may be linked to their increased risk for Alzheimer’s. Image Source

So if low estrogen is a risk factor for Alzheimer’s, could estrogen replacement therapy (ERT) combat this? ERT is commonly used as a treatment for menopausal symptoms such as hot flashes, as well as to reduce the risk of osteoperosis. Clinical trials investigating the effects of ERT on dementia have had mixed results. There is some evidence to suggest that it may only be protective if women begin treatment within the first few years of menopause. So far, the jury is still out on whether these therapies could be beneficial for preventing dementia. There are also some notable risks associated with ERT, including a higher chance of breast cancer.

What about male sex hormones? Similarly to women, men with Alzheimer’s disease tend to have lower levels of testosterone than normal. So if the loss of both sex hormones can increase the risk of Alzheimer’s, why do we see a much higher prevalence in women? One theory is that it relates to how quickly these hormones are lost. The menopause transition usually takes around four years, while male reproductive aging takes place gradually over several decades. Perhaps the abruptness of estrogen loss in menopause is responsible for the higher risk of dementia.

Another important difference between men and women lies in their risk for other dementia-related diseases. Women are more than twice as likely as men to have depression, and they also have a higher risk of insomnia and fragmented sleep. All of these conditions are linked to an increased risk of Alzheimer’s. In addition, women have historically been granted less access to education, employment, and physical exercise, which can be protective against dementia. This is particularly true for women who grew up in the mid-20th century and are now reaching their elderly years.

In conclusion, there’s still a lot we have to learn about why women are more prone to Alzheimer’s disease than men. In the meantime, both women and men can still greatly reduce their overall risk of Alzheimer’s through lifestyle changes. See 10 Tips to Reduce Your Dementia Risk to learn more.

 

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Why People with Down Syndrome are at High Risk for Alzheimer’s Disease

Down syndrome is a neurodevelopmental disorder caused by inheriting an extra copy of chromosome 21. The most common symptoms include intellectual disability, unusual facial features, and heart defects. About 1 in 700 babies is born with this condition.

The average lifespan for a person with Down syndrome is 60 years. Sadly, the last few years of their lives are often lost to Alzheimer’s disease. Nearly two-thirds of Down syndrome patients are diagnosed with Alzheimer’s before the age of 60. This is far higher than the general population, of whom less than 1% develop Alzheimer’s this early in life.

The reason for this greatly elevated risk of Alzheimer’s disease comes down to genetics. While chromosome 21 contains hundreds of different genes, a single gene is believed to cause Alzheimer’s disease in Down syndrome patients: APP. This gene encodes a protein called amyloid-beta. Amyloid-beta is a toxic, sticky protein that can clump together and accumulate inside the brain, which is believed to be a major contributing factor to Alzheimer’s disease.

Because of their extra copy of chromosome 21, people with Down syndrome produce more amyloid-beta than normal. Nearly 100% of Down syndrome patients start to develop amyloid-beta aggregates in their brains during their 40s. This puts them at a very high risk of developing Alzheimer’s at an early age.

After the practice of institutionalizing people with Down syndrome became less common, their life expectancy improved dramatically, up from only 25 in 1983 to 60 today. However, this means that more Down syndrome patients are living long enough to develop Alzheimer’s disease, which is a frightening prospect to these individuals and their families.

Despite the troubling statistics, there is hope for people with Down syndrome. Many neuroscientists believe that early intervention is key for preventing Alzheimer’s disease. However, ethical standards make it difficult to administer treatments to people before we know for sure that they’ll develop a disease, particularly if those treatments come with certain risks. This makes it challenging to test out new preventative therapies for Alzheimer’s disease.

Because of the very high rate of Alzheimer’s disease among Down syndrome patients, they may be an exception to this rule. New drug candidates can be tested on these individuals beginning early in life, which may prove to be a more effective strategy for preventing Alzheimer’s. While only time can tell whether these treatments will prove beneficial, many remain hopeful for the future of research.

 

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The New Definition of Alzheimer’s Disease Raises Ethical Dilemmas

A redefinition of Alzheimer’s disease could be a boon for clinical trials, but some warn that it could put patients at risk.

The current guidelines for diagnosing Alzheimer’s disease were established in 2011 by the National Institute on Aging and the Alzheimer’s Association. The guidelines, originally published in the journal Alzheimer’s and Dementia, focus on observable symptoms such as memory impairments, language problems, and personality changes.

However, the same group recently proposed a new set of guidelines based on biomarkers rather than symptoms. Biomarkers are physiological changes that can be easily measured and may be associated with a disease. For Alzheimer’s disease, the most widely-recognized biomarkers are amyloid-beta and tau, two toxic proteins that accumulate in the brains of people with this disease. The new guidelines propose that Alzheimer’s disease should be defined based on the presence of amyloid-beta and tau in the brain, without regard to cognitive symptoms.

This new way of defining Alzheimer’s disease brings with it both advantages and potential risks. In a recent Perspectives article published in Neural Regeneration Research, my colleagues and I discussed what the new guidelines could mean for the future of Alzheimer’s disease research and brought up some of the ethical dilemmas that it could pose.

Positive Aspects of the New Definition

The new way of defining Alzheimer’s disease offers several advantages, particularly for pharmaceutical companies. Most drug candidates for Alzheimer’s disease work by trying to get rid of amyloid-beta from the brain. Unfortunately, Alzheimer’s clinical trials have been a resounding failure for the past 30 years (see Where’s our cure to Alzheimer’s disease?). As a result, several pharma companies including Pfizer have shut down their Alzheimer’s research programs entirely.

Many pharma researchers believe that the reason these drugs failed is because they were administered too late in the disease’s progression. By the time Alzheimer’s disease is diagnosed, the patient’s brain is already full of large amyloid-beta deposits. But perhaps if we could administer the drugs to people in their 30s or 40s, when amyloid-beta has started to accumulate but cognitive symptoms are not yet apparent, they might be more effective.

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Clumps of amyloid-beta (shown in this illustration) can appear in the brain decades before the appearance of Alzheimer’s disease symptoms. Image Source

Under the current guidelines, these younger people who have amyloid-beta in their brains but no memory problems would not be considered to have Alzheimer’s disease. As a result, pharma companies would have to overcome steep legal issues in order to administer an experimental drug to people without a diagnosed disease. However, the new guidelines would allow these people to be diagnosed with Alzheimer’s, and thus they could be included in clinical trials.

This change would be great news for pharma companies, and possibly for the rest of us too. If they discover new drugs that can stop Alzheimer’s disease when administered at an earlier stage, it would be a huge breakthrough in preventing people from getting the disease. However, despite these advantages, there are some risks that we need to consider as well.

Ethical Issues with the New Guidelines

One of the biggest problems with this new definition is that many people who have amyloid-beta in their brains do not go on to develop the symptoms of Alzheimer’s disease. In fact, some studies suggest that as many as 1 in 3 seniors have enough amyloid-beta in their brains to meet the diagnostic criteria, yet they show no cognitive issues.

This discrepancy means that if we start diagnosing Alzheimer’s disease based on amyloid-beta alone, some people who receive the diagnosis in their 30s or 40s will never go on to experience any symptoms. Being diagnosed with a disease (particularly one that is currently incurable) can cause a substantial degree of anxiety and depression. There are ethical issues to be considered when we start diagnosing people with a disease they may never actually experience, causing undue stress for the patients and their families.

Another problem is that these asymptomatic individuals could be subjected to unnecessary treatments. In addition to the financial costs of such treatments, many Alzheimer’s clinical trials report adverse side effects, including increased rates of re-emergent infections and certain kinds of cancer. Treatments targeting amyloid-beta also increase the risk of ARIA (amyloid-related imaging abnormalities) by five-fold. ARIA is caused by tiny micro-bleeds in the brain’s blood vessels, which can result in confusion, headaches, and difficulty walking.

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Cerebral micro-bleeds from ARIA appear as abnormal white regions on this brain scan. Image Source

In redefining Alzheimer’s disease based on amyloid-beta, rather than the symptoms that actually affect patients’ lives, we will be subjecting many patients to unnecessary emotional hardship and potentially-harmful treatments. Whether the benefits to clinical trails are worth this sacrifice is a question worth careful consideration.

Does Amyloid-Beta Actually Cause Alzheimer’s?

In addition to the ethical problems that I’ve discussed, there’s a darker possibility that this new definition could severely derail Alzheimer’s disease research. For decades, the “amyloid cascade hypothesis” was widely accepted among neuroscientists. This hypothesis states that amyloid-beta is the initial cause of Alzheimer’s disease, and therefore we must get rid of it in order to cure the disease.

However, a growing body of evidence suggests that the amyloid cascade hypothesis could be wrong. For one thing, many people with amyloid-beta never develop this symptoms of Alzheimer’s disease, as I mentioned earlier. In addition, several studies suggest that amyloid-beta actually serves important roles in the brain and body (see The Villain of Alzheimer’s Disease Could Actually Be a Hero). For example, it may help the immune system to fight off infections by clumping around microbes and preventing them from spreading.

It’s possible that getting rid of amyloid-beta is the wrong strategy for fighting Alzheimer’s. And if that’s the case, then redefining Alzheimer’s in terms of amyloid-beta will only distract future research efforts away from the real path to a cure.

Concluding Thoughts

The advantages of the new definition for aiding future clinical trials are important, and they could help us discover treatments that are effective before the development of symptoms. However, we need to weigh this against the ethical risks of diagnosing asymptomatic people with Alzheimer’s, as well as the questionable validity of the hypothesis the guidelines are based on.

This debate should not be only left up to researchers and clinicians; I believe it is important that patients and their families also discuss this important issue and make their voices heard by the scientific community.

 

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What “Childhood Alzheimer’s Disease” Can Teach Us About the Brain

Niemann-Pick disease type C (NPC) is a condition you’ve probably never heard of. It’s an extremely rare disease, occurring in approximately 1 in 100,000 live births. But despite its rarity, the strange connections between NPC and a much more common condition, Alzheimer’s disease, are now leading researchers to consider how the connected mechanisms of these two diseases may help us in our search for a cure.

What Is Niemann-Pick Disease?

Children with NPC, including Addison and Cassidy Hempel shown in this article’s top image, typically appear normal until reaching middle to late childhood. Around that age, they begin experiencing subtle symptoms such as clumsiness, poor handwriting, and impaired speech. Some children lose the ability to move their eyes up and down or side to side. These problems gradually worsen over time, with affected children eventually losing the ability to speak or swallow. They may also develop seizures, involuntary muscle contractions, or other movement disorders.

Perhaps even more tragic than the physical symptoms are the effects of NPC on the brain. Children with this condition experience a progressive loss of memory and cognition, which has led to the disease’s unofficial name of “childhood Alzheimer’s disease.” Eventually, after a decline that can last many years, these children succumb due to respiratory failure or severe seizures. There is currently no effective cure or treatment.

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These images from the National Niemann-Pick Disease Foundation show the tragic progression of this disease in a child.

The Cholesterol Connection

NPC is caused by a mutation in one of two genes, known as NPC1 and NPC2. These genes are necessary for cells to be able to process and transport cholesterol. While cholesterol is often seen as something to avoid in our diets, we actually require a small amount of it to survive. Our cells need cholesterol to create new membranes or synthesize steroid hormones. When we consume cholesterol, it gets engulfed in cellular compartments called lysosomes, where it is processed and later released into the cell membrane. In people with NPC, cholesterol can’t be properly processed, so it gradually accumulates inside their lysosomes, especially within neurons. With all their cholesterol trapped, the neurons eventually begin to degenerate and die.

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This image shows the spleen of a patient with NPC. The white blobs are large accumulations of cholesterol. Image Source

NPC is an extreme example of what can happen when cholesterol metabolism goes awry. However, it’s not the only neurological disease that cholesterol plays a role in. People with Alzheimer’s disease, the most common form of dementia, tend to have higher levels of cholesterol in their brains than healthy controls. This may result in increased production of amyloid-beta, a toxic protein that’s considered one of the main causes of Alzheimer’s disease. Interestingly, patients with NPC also show increased levels of amyloid-beta in their cerebrospinal fluid, as well as the accumulation of tau (another toxic protein related to Alzheimer’s disease) inside their brains.

The connections between NPC and Alzheimer’s disease don’t stop there. Studies have found that mutations in NPC1 and other genes involved with cholesterol metabolism lead to an increased risk of Alzheimer’s disease. This suggests that cholesterol could be a key contributor to the neurodegeneration that occurs in both Alzheimer’s disease and NPC.

Where We Go From Here

Rare diseases like NPC are largely ignored by pharmaceutical companies, simply because they aren’t common enough for the research and development of a drug to turn a profit. While each of these diseases by itself is extremely uncommon, because there are thousands of different conditions out there, it’s estimated that 25 million Americans suffer from a rare disease. Most of these have no effective treatment.

Studying rare diseases may not be profitable, but they’re still incredibly important. As previously discussed in a fantastic SciShow video, rare diseases can often provide insight into the causes of more common conditions that share the same underlying mechanism. NPC and Alzheimer’s disease provide just one example of how researching cures for a disease that affects only a few thousand people worldwide could help us to learn about another condition that kills millions every year.

 

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How Music Impacts Alzheimer’s Patients

This article is a guest post by Carolyn Ridland, the founder of CaregiverConnection. You can read more about Carolyn at the bottom of this page.

It is challenging to watch a loved one go through problems with memory and thinking and exhibit behavioral changes that are characteristic of Alzheimer’s disease. Even more challenging is the fact that the condition develops very gradually until a point reaches where the patient cannot coordinate the normal day to day activities. While it might be impossible to treat the condition, there is a spectrum of therapies that have been suggested and deemed very useful in reversing the progression of the disease. One of these therapies is the use of music. Many people who have a loved one with the condition are glad to try anything that might work, but the important question is, how does music affect the function of the brain, and what impact will it have on a patient with Alzheimer’s?

How does Alzheimer’s affect the brain?

Most people think that Alzheimer’s and dementia, in general, are a regular component of the aging process. However, it is not a normal part of aging, despite that its greatest risk factor is age. There are people who start exhibiting symptoms of Alzheimer’s disease before they reach 65, which is known as early-onset. It is known that the brain typically shrinks with age, but it does not typically lose its neurons; this is not the case with Alzheimer’s patients. In fact, as they age, the neurons get destroyed, and this widespread damage makes most neurons lose their connections with each other, impairing metabolism, communication and repair (Jacobsen et al., 2015). The disease eats away at the brain function until the person can hardly function. While there is no known cure for Alzheimer’s, early detection and the use of the right therapies can help in slowing down the effects of the disease.

Music therapy for Alzheimer’s patients

Studies have shown that when patients who suffer from Alzheimer’s are led through songs that they recognize, their cognitive abilities are boosted, and they are able to recall memories and emotions tied to the songs. When participants with Alzheimer’s took a test on cognitive ability and life satisfaction, those that listened or sang during the test scored better in the test. Here are ways in which music could be beneficial to your loved one with Alzheimer’s.

Music evokes emotions that are attached to memories

Everyone has music pieces which are attached to very specific memories. These tied connections stay in the brain for decades, and the moment that the song is played, the attached emotions come flowing back, bringing with them the attached memories. Since a patient with Alzheimer’s is already having a hard time dealing with their memories, there is no better ways to trigger them than to play their favourite songs.

Musical aptitude and appreciation is the brain ability that stays the longest

As mentioned, people who suffer from Alzheimer go through a gradual loss of their cognitive abilities until their brain function completely deteriorates. However, the great news is that as the other abilities fade away, the ability to remember and appreciate music and the attached memories remains much longer than many others. This means that you can use music as a way of connecting with your loved one when they can no longer discuss their childhood or the memories which you made together. In addition, by playing music, you will make the person feel that they are still good at something, which makes them feel good.

Singing becomes a hobby

There is nothing that is more frustrating to a person with Alzheimer’s than the knowledge that they knew how to do something such as playing chess, but for some reason, they no longer can do it. Well, if your loved one’s condition has gotten to the point where they no longer remember these activities which they once used to enjoy, think about introducing music because it brings along fun games such as karaoke, sing along, and dancing games. Research shows that a simple act of watching music stimulates certain areas of the brain, which helps the patients exercise and polish their mind-power.

Music as a mood booster

People who have dementia tend to have a constant feeling of the blues and lots of episodes of stress induced agitation. Music has the ability to calm the listener’s nerves, elevate their mood and stimulate positive interactions with others. The good thing about music and especially the instrumental part of it is that it does not need a lot of cognitive processing, which means that it will not need a person with dementia to use their cognitive function to enjoy.

How to select the right music

The mental health and cognitive benefits that patients with Alzheimer’s get from listening to music are endless. It is therefore important to make sure that you include it in their daily routine. When choosing music for a loved one, always consider the following factors:

  • Consider the preferences that your loved one used to have. Using music as a mood booster will only work when the music is something the person can relate with.
  • To set the mood using music, play slow and mellow tunes when you want them to wind down and sleep. On the other hand, when you want them to get active, play faster beats.
  • Encourage movement when playing the music by inviting the person to dance with you or asking them to sing along.
  • When you are playing the music, try your best to cancel out all other sources of noise as you do not want to overstimulate their brain and agitate them.
  • Pay attention to the response which they give to each type of music. The response is what will guide you towards ticking the songs they like and eliminating those that they do not.

Those are a few important things to know about the use of music to help Alzheimer’s patients cope better with their condition and enjoy life. Keep looking for creative ways to incorporate music into their day to day life, and this may even help them hold on to their memories for an even longer time.

 

Middle Aged Woman Smiling With Hands On CheeksThis article is a guest post by Carolyn Ridland, the founder of CaregiverConnection. About 10 years ago, her parents began reaching the point where they could not be self-sufficient anymore. She was just married with two toddlers, so she felt like she couldn’t take them in, yet she wanted to make sure they were taken care of. Carolyn wanted to share her story, and to let others know that they are not alone if they are in a similar position. Children are expected to take care of their elderly parents when the time comes, but it’s not always that easy. Caregiver Connection emerged from a place of real love and compassion. They understand the struggle that exists when you care deeply about your loved ones, but you’re faced with decisions you never wanted to make. Their main message is that nobody should have to face these times alone.

 

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The Villain of Alzheimer’s Disease Could Actually Be a Hero

The toxic amyloid-beta protein has long been considered the cause of Alzheimer’s disease–but what if it’s actually been a hero all along?

If you were to look inside the brain of someone with Alzheimer’s disease, you’d immediately see that something has gone terribly wrong. The first thing you’d notice is that it’s much smaller than a healthy brain, appearing shriveled up like a raisin. Upon closer examination, you’d see that the brain is filled with large, dark clumps of protein. That protein, called amyloid-beta, can stick to itself and form toxic aggregates that poison the brain from within. Your first instinct would probably be the same as most scientists: in order to cure Alzheimer’s disease, we need to get rid of these amyloid-beta clumps.

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Artistic rendition of amyloid-beta plaques surrounding neurons in the brain. Image Source

It’s a reasonable assumption. These clumps of amyloid-beta, formally known as senile plaques, are among the most recognizable hallmarks of Alzheimer’s disease, and they’re toxic to brain cells in high doses. So it makes sense to think that getting rid of them will be the key for curing Alzheimer’s.

For three decades now, that’s exactly what scientists have been trying to do. They created drugs that targeted and destroyed amyloid-beta, or prevented it from being formed in the first place. They invented vaccines to help our own immune systems recognize amyloid-beta, and inhibitors that stopped amyloid-beta from sticking together to form toxic clumps. Yet, despite hundreds of scientists and billions of dollars devoted to the research, these efforts failed. Of the more than 200 drug candidates for Alzheimer’s disease that have reached clinical trials in the past 30 years, not a single one successfully cured the disease or slowed its progression. The drugs currently on the market for Alzheimer’s disease offer some patients a small improvement in their cognitive symptoms, but since they do not treat the underlying pathology, their effects are temporary and they cannot prevent the patient’s deterioration.

Even worse than the poor efficacy of these drugs were the severe side effects they often created. Many patients involved in these trials developed a condition called Amyloid-Related Imaging Abnormalities (ARIA), which results from leaky blood vessels bleeding into the brain. Other patients experienced dangerous infections or skin cancer, and a few even saw their cognition decline faster than patients who weren’t taking the drug at all.

The disastrous results of these clinical trials have shaken the field of neuroscience to its core. A few companies, including the pharma giant Pfizer, have even given up their Alzheimer’s research programs entirely. Yet I would argue that there is still hope for a cure to Alzheimer’s disease, and it lies by viewing the toxic amyloid-beta protein in a new light. In fact, I think that amyloid-beta might actually turn out to be a powerful ally in the fight against Alzheimer’s.

The Evolutionary Riddle of Amyloid-Beta

I’m a geneticist by training, and that means I think a lot about evolution. And so the first question that came to my mind when I first learned about amyloid-beta was, why do we have it in the first place? After all, the core premise of natural selection is that harmful traits tend to disappear from a population over evolutionary time. If amyloid-beta is nothing more than a toxic substance that makes us sick, then we’d expect it to become rarer as our species evolved, and eventually disappear completely.

Yet when you actually look at the data, the opposite seems to be true. In fact, every vertebrate species (including mammals, birds, and reptiles) produces a version of amyloid-beta that’s almost identical to our own. It’s even been found in sea anemones and hydra, meaning that amyloid-beta has been around for at least 600 million years.

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The hydra, a tiny invertebrate often found in ponds, has its own version of amyloid-beta. This suggests that the protein has been remarkably conserved across evolutionary time. Image Source

From an evolutionary perspective, this makes no sense. Why would a toxic, harmful protein have been conserved for so many years across such diverse species? The most likely explanation is that there’s more to amyloid-beta than meets the eye. Specifically, it must be serving some kind of beneficial purpose that’s caused it to be maintained for so long.

The idea that amyloid-beta could actually serve some kind of biological function was originally met with controversy, but as more evidence has emerged, the scientific community has begun to accept this shift in view. In fact, the more we look at amyloid-beta, the more functions we seem to uncover.

The Hero We Never Knew We Had

The beneficial roles of amyloid-beta have become something of a fascination for me. One of its coolest functions is within the immune system. Amazingly, the properties that allow amyloid-beta to aggregate into toxic clumps in the brains of Alzheimer’s patients can also be used to trap harmful microbes, preventing them from spreading. Once the microbes are stuck, amyloid-beta can kill them by tearing holes in their cell membranes. In fact, amyloid-beta’s chemical properties suggest that it’s part of a family of immune proteins called antimicrobial peptides, which all utilize a similar manner of clumping and ripping microbes to protect the body from infection.

In addition to its role in the immune system, amyloid-beta has many other functions. Some research suggests that it may suppress the growth of cancer cells, which could explain why people with Alzheimer’s disease tend to have a lower risk of developing cancer. Others propose that amyloid-beta could help prevent leaks in the brain’s blood vessels by clumping into a kind of “scab” that restricts bleeding. It also seems to be helpful in recovery from neuronal injuries, as mice that are unable to produce amyloid-beta have worse outcomes from traumatic brain injuries, spinal cord injuries, strokes, and even multiple sclerosis. Finally, recent evidence has suggested that amyloid-beta helps to regulate the signaling activity of neurons, which is extremely important for learning and memory.

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This figure, adapted from our recent publication in Frontiers in Aging Neuroscience, summarizes some of amyloid-beta’s possible roles in human biology.

In light of amyloid-beta’s newly-discovered functions, the side effects that occurred in Alzheimer’s clinical trials begin to make more sense. By removing amyloid-beta from the patients’ brains and bodies, these drugs may have inadvertently led to ARIA, infections, and other harmful outcomes.

A New Dawn for Alzheimer’s Research

So what do the beneficial roles of amyloid-beta mean for the future? Well, if the last 30 years of clinical trials tell us anything, it’s that our current approaches aren’t working, and the functions of amyloid-beta may explain why.

Of course, the fact remains that amyloid-beta is toxic to neurons, and it tends to accumulate within the brains of Alzheimer’s patients. But I would argue that getting rid of amyloid-beta outright is not the answer. Instead, we need to consider what might have caused it to start accumulating in the first place.

For example, maybe the amyloid-beta clumps are actually a protective barrier surrounding infectious microbes that have infiltrated the brain, or a scab that prevents blood from leaking into the brain. As we get older, brain infections and leaky blood vessels become more common, which might explain why amyloid-beta levels tend to increase over time. Perhaps after a certain threshold, the amyloid-beta that’s responding to these issues becomes more harmful than helpful to the brain. It’s doing its job too well–there are too many microbes or leaky blood vessels for amyloid-beta to clump around without its toxic properties damaging the brain in the process.

We can’t just get rid of amyloid-beta at this stage, because then the microbes or vascular leaks that it was protecting us from in the first place will be left unchecked. Instead, we need to first treat the underlying cause of the problem. Only once that has been resolved can we then go back with anti-amyloid-beta drugs and remove the toxic clumps from patients’ brains.

I want to be entirely clear here: at this point, everything I’ve said in this last section is pure speculation. We don’t know if all amyloid-beta plaques are caused by some other factor, or whether resolving that factor will make our drugs more effective. However, a few early studies have provided tantalizing hints that this hypothesis may be correct. For example, one study found that among Alzheimer’s patients who were infected with H. pylori, a common type of bacteria that causes stomach ulcers, treating this infection with antibiotics resulted in a 65% lower risk of Alzheimer’s progression after one year.

The study of amyloid-beta’s biological functions is still in its infancy, and we have a lot to learn about the true role that it plays in Alzheimer’s disease. But if additional research can confirm that amyloid-beta is a side effect of the disease instead of its root cause, it could usher in a new age of Alzheimer’s research and bring us one step closer to finding a cure.

 

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