COVID-19 and viruses

Author: Michael Butler, Ph.D. Neuroscience

Co-Contributor: Austin Van Decar, B.S. HPS, EMT

Introduction

Over the last few weeks there has been an unbelievable amount of misinformation being spread about the novel coronavirus that causes COVID-19 and what the world governments should do about it. The world seems extremely chaotic right now and everyone seems to be an infectious disease expert all of the sudden. While I’m not an infectious disease expert, or a virologist, epidemiologist, or a healthcare professional, I am a biological scientist. I have a PhD in Neuroscience and I work as a postdoctoral researcher at The Ohio State University Wexner Medical Center conducting research in Neuro-Immunology with a focus on nutrition and aging (disclaimer: this article is my own work and is not affiliated with OSU). Thus, I spend a lot of time reading about the immune system (usually how it impacts the brain) and have expertise in reading and interpreting peer-reviewed scientific literature. I am confident in my ability to help explain to my family and friends, and whoever else may read this, the science of what is currently happening in the world. In times of chaos, I usually find that correct information is comforting. In this article, I will attempt to summarize the basic biology behind the immune system, how it responds to threats like viruses, what a virus actually is, what a coronavirus is, how coronaviruses evoke an immune response, and what is special about the novel coronavirus that causes COVID-19 and the current pandemic that the world is dealing with.

Before we get to COVID-19, we need to go over some basic immunology. The human immune system is made up of two main parts: (1) the innate immune system and (2) the adaptive immune system.

The Innate Immune System

Some components of the innate immune system can actually be traced back to species that lived 500 million years ago. It’s been around a long time! It is made up of several different types of cells that all play a specific role in defending our bodies. The most famous cell of the innate immune system is the macrophage. Once a pathogen (something that is harmful to your body) enters our body, our macrophages are alerted to move towards the pathogen and destroy it. Here is an actual picture taken with an electron microscope of a macrophage destroying a bacterium.

Macrophages can recognize bacteria because the outside of bacterial cells are made up of fats and carbohydrates that are not natural to the human body. Macrophages have special receptors, which are proteins expressed on the surface of the cells, that can bind to these molecules and signal to the cell to destroy whatever they just came into contact with. While a macrophage is destroying something like a bacterium, it is also releasing specialized proteins called cytokines that are signaling to other macrophages and other types of immune cells that something is wrong and they may need help. In addition to the macrophage, the innate immune system contains several other types of cells that help out to destroy invaders, including natural killer (NK) cells (I think that’s an awesome name) that can destroy bacteria, parasites, some cancer cells, and virus-infected cells. Given that the world currently cares about viruses, I’ll say the innate immune system has some defense mechanisms against viruses when the virus is outside of a cell. With the help of different signaling mechanisms between innate immune cells (look up “the complement system” if you are interested in these signaling mechanisms), a virus can be engulfed and destroyed. However, as we will get to later, viruses actually enter the host’s cells and this is when the innate immune system is less effective and when we rely on the help of our adaptive immune system.

The Adaptive Immune System

The adaptive immune system is pretty unique to vertebrates (animals that have a spine), which includes all mammals and, of course, us humans! You may have heard of two types of cells that are pretty important for the adaptive immune system: B cells and T cells, both of which live in your lymph nodes and are called lymphocytes. B cells make and release antibodies. They have receptors on their surface that can sense very specific proteins on the surface of, say in this case, a virus. Once this contact happens, the B cell starts to make copies of itself over and over again for about a week until there are over 20,000 clones of that specific B cell that can all recognize the same antigen (the virus). Then they start making antibodies! Antibodies are similar to the receptor that initially found the virus but instead of hanging out on the surface of the B cell – they are actually released from the cell and stick to the virus. Other immune cells (like macrophages) will recognize the antibody-tagged virus and destroy it. This helps destroy pathogens that may otherwise be overlooked by the innate immune system. If viruses weren’t tagged with antibodies, some would go undetected. An antibody is like a GPS tracking device for pathogens!

However, this still does not solve the problem of when viruses get inside the host’s cells, which they need to do to reproduce. The adaptive immune system has a solution for that, though. T cells, specifically Killer T Cells (again, awesome name), can destroy cells that are infected with a virus so that both the cell and virus die together (the death of the cell is a good thing so it cannot further host the virus). They do this by receiving a signal from the infected cell and other immune cells and then making contact with that cell and signal for it to kill itself so the virus dies along with cell. It does sound rather sad but it is for the greater good of the entire organism, even if a few of its cells have to die in the process.

Viruses

Ok, so now that we have VERY general understanding of the immune system and a few of its few key players, let’s talk about why we’re all here – viruses – specifically, coronaviruses. A virus is a tiny pathogen that is only able to reproduce inside a living cell of a host organism. Viruses can infect all types of organisms, from plants to animals and even bacteria. There are several components of a virus. There is the genetic material that is made up of either DNA (like humans and other animals) or RNA. There is a coat of proteins that protect that genetic material and, in some cases, an outer layer of lipids (fats) called an envelope that further protects the virus (this is true for all coronaviruses). In order for a virus to replicate its genetic material, it needs to use the hosts’ cellular machinery. It does this by first attaching to the outside of the cell and penetrating through the cellular membrane. Once inside the cell, it sheds its protein coat to “release” its genetic material, which is then replicate by the cell’s own machinery. This is a cruel trick the virus plays on the host cell as the host cell is unaware it’s replicating viral (infectious) genetic material. Once replication of the genetic material has occurred, the new viral molecules are assembled in the cell and can be released (sometimes by literally exploding the cell open) to go infect other nearby cells.

Coronaviruses are a family of viruses. They are named for the crown-like (corona is Latin for crown) structures on the surface of the virus (pictured below).

There are several different strains of coronaviruses and 4 of them are common in humans. In fact, these 4 strains of coronaviruses (along with rhinoviruses) are the main causes of the common cold. It is important to point out that the common cold is different from the flu, even though the two terms are often used interchangeably. One does not have the flu unless they are actually infected with a strain of the influenza virus. Anyway, I digress. In humans, coronavirus cause an upper respiratory infection and are very common and normally pretty mild (hence the common cold). Humans are used to seeing the main 4 strains of coronavirus and our immune system does a pretty efficient job of clearing the virus and returning us to normal.

However, back in 2002 a new coronavirus was discovered, meaning this virus was genetically different from the other 4 strains previously known to infect humans and it was one that the human immune system had never been trained to defend against (remember that antibodies are made for killing pathogens AFTER being exposed to their specific receptors). This new virus was called SARS-COV and caused the Severe Acute Respiratory Syndrome (SARS) pandemic. Anytime a new virus infects a species it is alarming and needs to be taken seriously. Now, SARS-COV wasn’t technically a brand new virus – it was just new to humans. It had been reproducing in other animals (like bats) for a long time. Viruses evolve to reproduce in certain host species and cannot reproduce in other types of hosts. However, every now and then a zoonotic virus comes along. A zoonotic virus is one that can jump from a different animal species to the human species. This is alarming because normally viruses don’t really want to kill their host (unless that’s part of their replication mechanism but we don’t have the time for that in this article) because that means they die too. Thus, when a virus jumps to a different species it doesn’t normally reproduce in, it could have some terrible, unintended effects (death) on that new species. The SARS virus had an ~10% mortality rate and caused a severe illness in those who were infected. This actually made it easier to contain because it was easier to recognize, track, and isolate. The same was the case for Middle East Respiratory Syndrome (MERS), which had an even higher mortality rate of ~35%. This was also a zoonotic coronavirus that likely came from camels. So until recently there were 6 different coronaviruses that could infect humans (2 of which originated in other species), some producing worse effects than others.

Then comes COVID-19 (coronavirus disease of 2019) at the end of last year. The viral strain is officially called SARS-COV2 and the disease it produces is COVID-19. This is the 3^rd type of coronavirus that made the jump from a different species to humans. While it is still unclear, scientists suspect that SARS-COV2 made the jump from bats to pangolins (a scaly ant-eater-like animal) and then to humans. It is believed this originated at an exotic animal market in Wuhan, China, which is where the outbreak began at the end of 2019. This virus causes an upper respiratory tract infection (like other coronaviruses) and is usually accompanied with a fever and body aches. So far, the mortality rate is hard to calculate as it has been extremely difficult to get an accurate number of total cases. Another important factor contributing to not being able to track the virus is that the symptoms can actually be very mild, much less severe than SARS or MERS. Because of this, some people may not even know they have it, but can still spread it to others who may not be so lucky.

Coronaviruses and the immune response

Coronaviruses are respiratory viruses, meaning they like to infect tissues of the respiratory tract (nose, throat, lungs, etc). When they get into the human body they bind to cells in these tissues and penetrate the cells just like I talked about before. Coronaviruses seem to be able to infect immune cells of both the innate and adaptive immune system, which is a pretty good viral strategy if they are able to suppress both the innate and adaptive immune response. However, the immune system typically responds within enough time to clear the virus. The typical immune response you probably think of is a fever, increased congestion due to increased mucus buildup, coughing, body aches, etc. These are all adaptive responses we experience to help get rid of a pathogen, in this case a coronavirus. Increased body heat can be unfavorable to a pathogen, increased mucus can help trap certain pathogens, and body aches can help us retreat and withdraw so our body can devote all energy to fighting the pathogen.

Immune function varies across the lifespan (this is where some of my actual research and expertise comes in!). As humans age, our immune system gets into a hyper-reactive state and we have a higher baseline level of inflammation (immune activity) in our bodies. This is low-grade inflammation in the absence of any disease or pathogen. Aging is accompanied by an increased number of certain innate immune cells as well as increased pro-inflammatory cytokines that are constantly sounding the alarm to the entire immune system. This increased baseline activity of the aging innate immune system results in an exaggerated response to any secondary challenge to the immune system (secondary meaning in addition to aging). This can come in the form of a virus, bacterial infection, or, in the case of my own research, even unhealthy diets. In addition to hyper-reactivity, the aged immune system is also less efficient at clearing pathogens from the body, resulting in prolonged immune activity and failure to resolve the inflammation. This is likely why we see the most severe cases of any bacterial or viral disease in older people. Their immune systems are hyper-reactive and so overwhelmed they eventually succumb to the invasion. The opposite is thought to be true for younger people: the immune response is appropriate because it is not already heightened at baseline, the immune system is efficient at clearing pathogens, and inflammation is resolved in a timely fashion.

If you take nothing else from this article, just keep re-reading this paragraph and the one before it. The elderly are the most vulnerable during this global pandemic. Most people under 50 or 60 will be able to handle this virus without much complication, though there are exceptions. Actually, new data from the CDC says as many as 1 in 5 people ages 20-44 who contract COVID-19 will need to be hospitalized. However, only 0.2% end up dying, which is higher than the flu. The older a person is, the less likely they are going to be able to fight off SARS-COV2. Also, I should point out that even in the elderly, most patients recover, statistically speaking. But the mortality rate is much higher as a person ages. In addition to the elderly, individuals with underlying conditions such as heart disease, lung disease, or diabetes are also at a greater risk of death from COVID-19 (see charts on COVID-19 mortality rates below).

Potential treatments

While traditional antiviral drugs used to treat the flu are not effective against COVID-19, there have been a few reputable reports of antiviral drugs that have shown some efficacy against it. Unlike the flu, there is no approved, effective vaccine for SARS-COV2 or any other coronavirus. However, at the time of writing this article the U.S. has started a Phase 1 clinical trial for a SARS-COV2 vaccine, which was created in record time. It will still take at least 12-18 months to conduct the clinical trials and for it become approved for mass use like the influenza vaccine. Given the limited medical interventions available to prevent or treat COVID-19, the world must turn to behavioral interventions to stop the spread of the virus. This means – you guessed it – social distancing. The SARS-COV2 virus spreads via respiratory droplets. When a person carrying the virus coughs or sneezes these droplets containing the virus land on surfaces and can live on certain surfaces for days. When someone else touches that surface and then touches their face, they are now infected. This is why constantly washing your hands is so important. Also, social distancing is a proven method to stop the spread of an infectious disease and is done so to protect the most vulnerable and to not overwhelm the healthcare system. Limited interactions prevent viral transmission. It’s a technique that has been around for centuries and it’s simple and effective.

The U.S. does not have enough hospital beds or medical supplies to treat hundreds of thousands (maybe more) of patients needing hospitalization due to COVID-19 in general, and especially not on top of an already active flu season and other ER and ICU patients needing treatment for various issues. Furthermore, the U.S. is a generally unhealthy population with two-thirds of the country being overweight or obese and high rates of heart disease and diabetes. We are arguably the most unhealthy nation to be heavily impacted by this virus. An already unhealthy population and an unequipped healthcare system is a bad combination when a new pandemic occurs.

After a few months of extreme social distancing in China, their epidemic seems to be letting up and life is slowly getting back to normal. During the outbreak of the 1918 Spanish Flu in the WWI fronts, the practice of distancing soldiers in medical wards was mandated. Some medical historians argue that distancing soldiers with the Spanish Flu had a huge impact on the outcome of WWI. History shows us that there is hope, and between science and medical advancement we will see the other side of this pandemic.

Not all of us can know everything. As a scientist, I constantly have to rely on the expertise of other scientists we collaborate with. Just like they rely on me for my expertise. If you hear scientists and doctors, actual infectious disease experts, telling you this is serious, listen to them. It is time every single person in the United States takes it seriously. The quicker you do, the quicker we can beat this virus and get back to normal.

Acknowledgements:

I’d like to thank Austin Van Decar, a friend and medical historian, for providing thoughtful feedback and suggestions for this article.

References:

Barman, S., Ali, A., Hui, E.K., Adhikary, L., Nayak, D.P., 2001. Transport of viral proteins to the apical membranes and interaction of matrix protein with glycoproteins in the assembly of influenza viruses. Virus Research. 77(1):61–69. doi:10.1016/S0168-1702(01)00266-0. PMID 11451488.

Isomura, H., Stinski, M.F., 2013. Coordination of late gene transcription of human cytomegalovirus with viral DNA synthesis: recombinant viruses as potential therapeutic vaccine candidates. Expert Opinion on Therapeutic Targets. 17 (2): 157–66. doi:10.1517/14728222.2013.740460. PMID 23231449.

Lim, Y., Ng, Y., Tam, J., Liu, D., 2016. Human Coronaviruses: A Review of Virus–Host Interactions. Diseases 4, 26. doi:10.3390/diseases4030026

Sompayrac, L., 2012. How the Immune System Works. Wiley-Blackewll.

https://thehill.com/policy/healthcare/488325-cdc-data-show-coronavirus-poses-serious-risk-for-younger-people?fbclid=IwAR1F2wFOnzxAMEn28_9oC6ZVeAgRnBDLO5TG7lUSZYmNY49bGjsS8VQm0Ug

Images taken from:

cdc.gov

https://www.worldometers.info/coronavirus/coronavirus-age-sex-demographics/

Sompayrac, L., 2012. How the Immune System Works. Wiley-Blackewll.

https://www.quora.com/What-is-the-relationship-between-antibodies-and-B-cells

https://www.washingtonpost.com/health/2020/03/10/social-distancing-coronavirus/

March 19, 2020 0

This Is Your Brain On Alzheimer’s Disease

Introduction

Alzheimer’s Disease (AD) effects approximately 24 million people worldwide and that number is set to increase as the population continues to get older. Despite its prevalence, there is no effective treatment routinely practiced for AD. This is mainly due to the lack of understanding regarding the exact biological mechanisms of the disease. The purpose of this article is to explain how a functioning nervous system normally operates, how AD disrupts that normal operation, the current understanding of the pathology of AD, and some lifestyle interventions everyone can use to reduce the risk of developing AD.

The brain

The brain is made up of billions of cells that communicate with one another to give rise to all the complex emotions and behaviors we display as humans. The “main” cell type in the brain is a specific type of brain cell called the neuron. For all intents and purposes, neurons are similar to every other cell type in the body. They have a nucleus that contains all of your genes located on strands of your DNA. They have ribosomes that help produce proteins. They have mitochondria that produce energy for the cell. And they have the ability to excrete molecules that function as signals to communicate with other cells nearby. It just so happens that the pattern in which these specialized cells communicate produces an array of consequences such as complex behavior, consciousness, a sense of self, language, and emotions. A resting neuron holds a certain electrical charge. To become activated, a positive shift in the electrical charge has to occur and when the voltage reaches a certain threshold, the neuron releases molecules that travel across the space between two neurons until it reaches a second neuron. Once this molecule reaches a second neuron it will bind to a receptor located on the surface or inside of the second neuron and, depending on the type of molecule, change the electrical charge and cause the second neuron to become either activated or inhibited. These cell-to-cell interactions are called synapses. A collection or specific sequence of synapses are what make up circuits in the brain. The communication between these individual cells in these circuits are what ultimately produce the complex thoughts and actions we display as people.

In the human brain there are approximately 80-100 billion neurons that produce over a trillion synapses. To further complicate the system, the brain contains an equal number, and by some estimates an even greater number, of other cell types called glial cells that serve their own specific functions. Two of the most abundant glial cells are called microglia and astrocytes. Microglia are the brain’s innate immune cells and protect the brain from viruses, traumatic brain injury (like a concussion), or some other harmful stimuli. Microglia can also function to provide support for neurons and their many synapses and help with clean-up of cellular debris produced throughout the day. These cells have two-way communications with neurons and are integral to a healthy functioning brain. Astrocytes can also provide immune and synaptic support but serve a variety of other functions. Given the hundreds of billions of cells in the brain and the trillions of communications between them, it is not hard to comprehend how easy it is for something to go wrong. When communication between cells go wrong you can get dysregulated thoughts and behaviors. Brain malfunction can happen at many stages in life. Most commonly these malfunctions occur during child development and adolescence when the brain is still being “set up” or in later in life as an individual ages and the brain starts to “break down.” Over the years physicians and psychologists have given labels to common symptoms of brain malfunction. Some of the more well- known labels include depression, anxiety, schizophrenia, autism, bipolar disorder, etc.

Due to the complexity of the brain described above, it is generally difficult to treat brain disorders with great success. However, using simpler models such as animals (typically mice or rats) or cell cultures (cells in a Petri dish) to systematically design experiments to tease apart biological mechanisms of brain function has provided some key insights to how these disorders occur and what we can do to fix them. One common disorder that occurs later in life is Alzheimer’s disease (AD). In the next section I will talk more in depth about AD, specifically, and what is known to go wrong in the AD brain.

Alzheimer’s disease (AD) background

Generally speaking, AD is classified as a chronic neurodegenerative disease that progressively worsens over time. The earliest symptoms typically include short term memory loss but, as the disease progresses, symptoms extend to include disorientation, language problems, mood swings, and overall personality shifts. Ultimately, as the brain continues to deteriorate, this can put patients at a greater risk of developing other deadly health concerns. Though it can vary, the typical life expectancy after diagnosis is 3-9 years. The following paragraphs will attempt to break down the biology of what is happening as AD develops.

When compared to other types of dementias, a characteristic unique to AD is the presence of amyloid plaques and tau tangles in the brain ¹. Amyloid plaques are aggregates of the amyloid beta protein that accumulate outside of neurons. Amyloid beta is produced in healthy individuals as well, though the primary function is still unknown. However, in a diseased brain, the “clean-up” of amyloid beta is impaired and these proteins accumulate to form the plaques present in an AD brain. It is thought that these plaques become toxic to the surrounding neurons and induce a programmed cell death called apoptosis.

Another major player in AD pathology are tau proteins. Tau proteins have a specific known function in the healthy individual. While expressed in other cell types, they are mainly expressed in neurons and are essential building blocks of microtubules, which offer structure and support to cells. In a diseased brain, tau proteins become damaged and start pairing with other damaged tau proteins and form “tau tangles.” One prevailing hypothesis is that when these tau tangles form, it destroys the cell’s structure causing the neuron to essentially collapse and eventually die.

In cases of amyloid beta and tau, it is thought that the accumulation of proteins become toxic and over time results in the death of individual neurons. In AD, this type of pathology becomes first noticeable in an area of the brain called the hippocampus. The hippocampus is crucial for the conversion of short-term memory to long-term memory and learning. When one neuron dies, it breaks a link in the circuit. The brain is extremely adaptable and can handle the loss of a few cells at first. However, as more individual cells in the circuit continue to die, memory will start to decline. Eventually this pathology will spread to neighboring parts of the brain causing the array of symptoms described above.

Despite all that is known about the pathology of AD, the underlying cause is still debated. Just because an increase in amyloid plaques and tau tangles are correlated with the progression of AD, it does not mean they are the root cause. In fact, these proteins are not inherently toxic to neurons. If they were, the cell would not produce them. Scientists even hypothesize that tau and/or amyloid beta may be protective, at least initially. The hypothesis is they are produced to compensate for some other unknown insult to cellular health. There is some scientific evidence for this but conclusive data and consensus is lacking within the field of AD research.

AD and brain inflammation

In recent years, it has become clear that brain inflammation, a.k.a. neuroinflammation, is another pathological hallmark of AD ². In general, neuroinflammation is initiated by microglia (the brain’s immune cells) in response to both the initial cause of cell injury (maybe amyloid beta and tau tangles) as well as the dying cells resulting from that insult. If brain tissue health is not restored, then neuroinflammation can become chronic and erode the surrounding tissue by continuously releasing inflammatory molecules. It is true that in regions of the brain most effected by AD, there is a significant increase in activated microglia, as well as astrocytes, which also have some immune function.

In AD, the hypothesis is that the increased accumulation of amyloid beta plaques and tau tangles stimulates a chronic inflammatory reaction to clean up the debris. Chronically activated microglia releasing inflammatory molecules can kill neighboring neurons. This inflammatory response can actually perpetuate a vicious cycle, causing more amyloid beta buildup, more inflammation, and more cell death. Indeed, animal studies have shown that inhibiting chronic neuroinflammation has a positive outcome on learning and memory in rodents, as well as prevents neuronal death. The inflammatory pathology of AD and other neurodegenerative diseases is a growing field in neuroscience. Current research, including the research I do at Ohio State, is investigating the hypothesis that microglia may not function normally during natural aging and what cellular mechanisms and environmental factors may be driving these changes. It is also becoming increasingly clear that many lifestyle factors, such as diet and exercise, can have major impacts on microglial function and memory as we age.

Preventing AD

If everything up until now sounds bleak, there is some good news. Recent scientific evidence suggests that AD risk can be decreased if the right steps are taken early on. In the past, pharmaceuticals were the most common treatment option for individuals with AD. Billions of dollars have been spent and hundreds of drugs have been developed with little success. The complexity of the brain and underlying mechanisms leading to cell death contributes to the poor success of pharmacologically fighting AD. In recent years, research has begun to investigate the role of lifestyle in developing AD and has identified ways to be proactive in reducing your risk of developing AD and slowing AD progression by implementing lifestyle changes.

Having good overall health is critical to preventing AD. In fact, good overall health is vital for brain health in general. The brain is an organ. It is an organ in the same way the heart is an organ. Or the liver. Or the pancreas. Or the lungs. You get the point. Brain health, or “mental” health, is just health. In the same way you are told to take care of your heart or your lungs or your liver, you should be being told to take care of your brain. The good news is, research suggests the same things that are good for your body are also good for your brain. The basic lifestyle habits we can develop to promote optimal brain health and reduce the risk of AD revolve around sleep, exercise, and diet.

Sleep is crucial for a healthy brain. During sleep, your cells, including neurons, enter a state called autophagy, in which the cell’s waste removal system is activated and begins clearing out excess proteins and damaged cellular components that accumulated throughout the day ³. Removal of these excess cellular components promotes cell survival by conserving energy. This is one of the primary benefits of sleep. Data suggest ~ 8 hours of sleep per night is ideal for the average adult human and is an important lifestyle factor to maintain for optimal brain health and AD prevention. A lack of sleep can result in less cellular clean-up and eventual protein accumulation, including amyloid beta, which can become toxic as described above.

Just like exercise is good for the lungs, heart, and other muscles, it is also good for your brain. Exercise has been shown to increase levels of neuroprotective chemicals, reduce chronic inflammation, and reduce signs of aging. It has also been shown to improve cognitive tasks and memory ³. All of these will lead to a decreased risk for AD.

One of the biggest lifestyle factors for brain health and AD risk is diet ³. Diet has an overwhelming impact on all bodily functions and the brain is no exception. In a few recent clinical trials, dietary changes were a huge component of AD treatment. In general, data suggest that diet should be plant-rich. This means lots of fruits and vegetables. Being vegetarian is not a necessity but dramatically limiting your meat and poultry consumption is important, particularly red meat. While still debated at times, the general consensus is that red meat consumption has been associated with negative health outcomes ⁴. In particular, saturated fatty acids, which are very high in red meat, has been shown to be pro-inflammatory in both the systemic immune system and the brain. A chronic saturated fat-rich diet leads to chronic immune activity in the brain, increased neuronal stress, and eventual cell death. Diets high in saturated fat (and sugar!) have been shown to lead to neuroinflammation and cognitive decline ⁵. This cognitive decline can be reversed in animal studies by inhibiting inflammation. In humans, saturated fats and obesity are huge risk factors for AD development. Interestingly, unsaturated fatty acids have been shown to be anti-inflammatory. Thus, consumption of foods high in unsaturated fats, such as fish, nuts, and oils (like olive oil) are encouraged for the maintenance of a healthy brain. Another important aspect of diet is timing of food consumption. There is a large literature suggesting that time-restricted eating has many positive health benefits for the brain. Eating within an 8-10 hour window, and not eating within 3 hours before going to sleep, have shown positive health benefits, including anti-aging effects in the brain and immune system ⁶.

Another important aspect of diet and overall brain health is your gut microbiota. The gut microbiota is the population of bacteria that live in your gut. In the average human body, there are more bacterial cells than human cells. In fact, the majority of these bacterial species are critical to our health. In the gut, bacterial cells live off of the food we eat and in return they release metabolites that are important for regulating our immune system and communicating with our brain ⁷. Since our gut bacteria eat what we eat, our diet plays a huge role in the proper functioning of our gut bacteria. Important nutrients for gut bacterial health are complex carbohydrates and fiber. Thus, eating foods high in fiber and whole grains is recommended. Overall, having a healthy, daily mix of fruits, vegetables, grains, fiber, and unsaturated fats (fish, nuts, oils) will result in a healthy immune system, a healthy gut, and optimal brain health. This, along with adequate sleep and regular exercise will greatly reduce the risk of AD. Simple, right?

Conclusion

For decades everyone has been told to “eat right”, get sleep, and exercise regularly. The only difference is no one realized those rules were also good for your brain. And now, with new insights and understandings of how integrated the brain is with the immune system and rest of the body, scientists are beginning to reveal the mechanisms of how lifestyle effects brain health. While the above lifestyle changes will impact AD risk, it can also be extended to other disorders of the brain. Increased immune activity and diet, sleep, and exercise have been implicated in almost every brain disorder, including mood disorders, schizophrenia, and autism. Due to advances in science and modern medicine, people are living easier and longer than ever before. In the Western world, there has never been more food readily available for easy preparation and consumption than there is right now. As technology improves many aspects of our lives, it promotes a more sedentary lifestyle with limited physical exercise and disrupts our sleep patterns (how often do you lie in bed at night watching TV for hours?). It is helpful to recognize how these issues contribute to impaired brain health and overall health and then implement practices to help mitigate these outcomes. Until brain health or “mental” health is viewed as the same as health, there will always be a stigma surrounding disorders of the brain.

AD is a perfect, yet unfortunate, example of what happens when you slowly start to take away parts of the brain. It completely changes a person. Their moods, their inhibitions, their motivations. You are your brain and it needs to be taken care of, just like the rest of your body. Hopefully this article has not bored you to death and you have reached the end with a better general understanding of how the brain functions normally and what goes wrong in AD. To sum up, the brain functions in circuits of neurons and other cell types communicating with each other. When mechanisms of cell function and protein removal start to break down, neurons die, resulting in impaired brain function and cause dramatic behavioral shifts. These symptoms and pathology can be mitigated by lifestyle interventions such as an anti-inflammatory diet, adequate sleep, and regular exercise.

References:

Ittner, L. M. & Götz, J. Amyloid-β and tau — a toxic pas de deux in Alzheimer’s disease. Nat. Rev. Neurosci. 12, 67–72 (2011).
Rubio-Perez, J. M. & Morillas-Ruiz, J. M. A Review: Inflammatory Process in Alzheimer’s Disease, Role of Cytokines. Sci. World J. 2012, 1–15 (2012).
Pistollato, F. et al. Associations between Sleep, Cortisol Regulation, and Diet: Possible Implications for the Risk of Alzheimer Disease. Adv. Nutr. An Int. Rev. J. 7, 679–689 (2016).
McAfee, A. J. et al. Red meat consumption: An overview of the risks and benefits. Meat Sci. 84, 1–13 (2010).
Miller, A. A. & Spencer, S. J. Obesity and neuroinflammation: A pathway to cognitive impairment. Brain. Behav. Immun. 42, 10–21 (2014).
Mattson, M. P., Longo, V. D. & Harvie, M. Impact of intermittent fasting on health and disease processes. Ageing Res. Rev. 39, 46–58 (2017).
Singh, R. K. et al. Influence of diet on the gut microbiome and implications for human health. J. Transl. Med. 15, (2017).