Cobbers on the Brain

Alzheimer‘s disease or AD is a degenerative disease that leads to memory loss, and decline of cognitive functions. Type 2 diabetes (T2D) is caused by problems due to insulin resistance. How are these two different diseases related? Is glucose regulation related to neurons dying? Research has shown that having type 2 diabetes is a major risk factor for AD, and vice verses. These two diseases are more alike than they appear. The inflammation and insulin pathway are two molecular mechanisms that explain the correlation between the two diseases.

 The Insulin Pathway

In order to understand the insulin pathway we must first talk about insulin resistance. This resistance takes place in both AD and type two diabetes.

Type 2 Diabetes: In order to breakdown glucose the body needs insulin. In T2D insulin does not work properly. This leads to high levels of glucose in the body, which causes high blood sugar. Having problems with insulin production can lead to other problems in the body, like in the brain for example.

 Alzheimer’s: Insulin resistance can be shown in postmortem brains of people who suffered from AD. This impaired insulin signaling can be seen clearly in the hippocampus region of the brain. It is thought that insulin resistance in an AD brain may be caused by the build up of amyloid beta plaques. However, this is one hypothesis. There are many more hypotheses being developed surrounding the topic of insulin resistance in the brain.

Inflammation

Insulin resistance plays a large role in the inflammation found in type 2 diabetes, and AD.

Type 2 Diabetes: Obesity, due to poor diet is often linked to the development of insulin resistance, and ultimately T2D. When fat cells accumulate, inflammatory cells follow. One of the main inflammatory cells involved in T2D is the cytokine TNF-α. 

Alzheimer’s: Chronic inflammation is one of the characteristics of AD. The inflammation seen in AD is caused by the immune cell called microglia. The microglia are responsible for the protection and remodeling of synapses in the brain, and help contribute to neuroplasticity. Microglia often produce inflammatory cells in response to increased accumulation of amyloid beta plaques. Research has shown that in order for amyloid beta to cause insulin resistance, and therefore inflammation the cytokine TNF-α must be present.

What does this have to do with my diet?

Our society values convenience, so when given the choice between fast food and taking the extra time to pack food it is not surprising that many of us would choose the fast food option. These poor dietary choices combined with spending your free time watching Netflix can lead to serious problems. Nearly 40% of Americans are obese, and 30% of those who are overweight or obese have type 2 diabetes. While maybe these statistics alone aren’t enough to change your mind maybe this next statistic will make you question whether that extra piece of cake is truly worth it. Having T2D doubles your chances of developing Alzheimer’s Disease. Now I am not saying to ditch fast food entirely, I enjoy treating myself too, but the next time I am given the option of packing my lunch or get fast food, I’ll be packing my own.

 Why should you care?

There is no cure for Alzheimer’s Disease, so it is important to take preventative steps now. Remember, little changes can make all the difference.

• Pack a meal for on the go instead of getting fast food
• Watch TV or Netflix while you work out
• Find health snacks that you enjoy
• Take time for yourself!! Whether it by cooking dinner, or working out try to find healthy practices to implement now. Trust me, your future self will thank you.

Image 1  https://www.psychologytoday.com/us/blog/diagnosis-diet/201609/avoiding-alzheimer-s-disease-could-be-easier-you-think

Source: https://www.ecowatch.com/dr-mark-hyman-why-scientists-now-call-alzheimers-type-3-diabetes-1882174730.html

Alzheimer’s Disease (AD)

Alzheimer’s Disease (AD) is seen throughout popular culture today and is one of the most well known neurodegenerative disease there is. AD is the most common type of dementia, and is what most people often associate the disease with. Symptoms of AD include memory issues, confusion, problems speaking and writing, alterations in mood and personality. Despite how prevalent AD is and how much research is been put behind it, there is still very much that is not known about the progress of AD and why individuals with AD are being affected.

Neurofibrillary tangles

In understanding AD there are several aspects of disease that are essential to bigger picture. Neurofibrillary tangles (NFT) are one of these. In AD one of the major issue that occurs is proteins in the brain called Tau are hyperphosphorylated. This is one of the markers that is used to diagnose AD, as the malformed Tau proteins build up there is so malfunction associated with the cells. Exactly how this happens in not known but scientists are investigating how NFTs are directly associated with AD. It is believed that some or most of the communication between neurons are blocked because of these.

AB plagues

Amyloid is often used to describe proteins that are naturally produced by the body. The specific amyloid that is observed in AD is referred to as beta amyloid (BA) and is built up because the of incorrect cutting on amyloid precursor protein (APP). This incorrect cutting causes there to be longer BA in the brain which accumulates together to form plaques that cannot be broken down.

Figure 1: This image depicts the two most common identifiers of AD in the brain. There is also an observed loss of mass of brain mass, especially in the hippocampus which is an area associated heavily with memory.

Source: http://weeklyhealthtip.blogspot.com/2015/11/the-link-between-type-2-diabetes-and.html

What else do we know?

One of the major players scientists associated with AD are the cytokines of the immune system. Inflammation is seen in individuals who have AD and the response of the immune system to lower this inflammation is to send in cytokines. These are cells that have response on another cell, in this instance to give a response to inflammation. Thinking about the relationship between AD and cytokines is much like pondering the age old question of the chicken and the egg. Increased amounts of cytokines are associated with mutated APP molecules and Tau phosphorylation and eventually leads to neuron death which is a major culprit in neuroinflammation. So was it the inflammation and BA plaques that called the cytokines or excess cytokines that started the inflammation? A bigger question lays behind this, why is there a strong relationship between AD and type 2 diabetes? What about the two strings them together?

Type 2 Diabetes (T2D)

What is it?

Type 2 Diabetes (T2D) which is also known as adult onset diabetes, is when the body no longer processes glucose properly because of insulin resistance or the lack of the production of insulin. Insulin is the molecule in the body that is response for regulating the sugar molecule glucose in and out of the cells. Although T2D is more common in adults, as childhood obesity increases so does the chance of developing the disease. There is no cure for T2D but can be regulated through healthy eating and exercising.  

Figure 2: The connection between the brain and body is undeniable but eating healthy not only helps with the regulation of T2D it also increases the overall sense of wellbeing and may help the brain in the long run, much longer than some people may think.

Source: https://www.medindia.net/patients/lifestyleandwellness/diet-and-alzheimers-disease.htm

Diet and Diabetes

As seen through ways to live with T2D, diet plays a large role. It is important for individuals with T2D to take insulin shots to increase the amount of insulin in the body but in addition to this, as stated above, taking careful notice of the food that you put into your body. As seen with younger individuals, those who experience or are on the verge of obesity are at risk of developing T2D, suggesting there is some relationship between T2D and food associated with obesity. Although the exact reason for T2D diabetes is unknown to researchers there is some evidence to suggest that weight gain and unhealthy eating are apart of the cause. What most people don’t associate with this however, is AD even though there is a clear link between the two.

Figure 3: A venn diagram shows the relationship between T2D and AD by comparing the similarities between the two. As seen above, there are more things in common than many people realize. The major classifiers of AD are seen listed as well but are not observed in T2D.

Source: https://www.mdpi.com/2072-6643/7/9/5341

Insulin in Alzheimer’s Brain: Type 3 Diabetes

Insulin is so well known in the development of T2D, as well as type 1, that many people do not often realize that it plays a major role in other parts of the body, including the brain. Insulin can increase spatial memory, is essential in cognitive and memory functions, as well as influencing feeding behavior. In patients with AD less insulin is seen as well. There is also a correlatory 80% of individuals who have AD also have insulin resistance of T2D, prompting AD to be called type 3 diabetes. Although there is much more research required behind this notion, scientists urge individuals (especially those with T2D or at risk of developing it) to eat better.

Another culprit in the development of both diseases is leptin. Leptin is a hormone that is made by the body to regulate caloric intake and feeding behaviors. In one study in particular, researchers found that there mice with high fat diets did not allow leptin to bind to neurons which never alerted the body that it was full and the mice continued to eat until they were overweight. Leptin also plays a role in the insulin pathway in the brain. Mutated leptin pathways often led to insulin resistance in individuals. This suggests that high fat diets that change the structure and purpose of leptin are not only associated with diseases related directly to insulin, such as T2D, but others like AD that have less information but what is known is the lack of insulin in the brain. This shows that there is no one common link between the three but rather may remain interconnected to each other.

Figure 4: Many individuals with T2D or at least insulin resistance are at risk of developing AD.

Source; https://ediblearia.com/2016/09/11/alzheimers-disease-is-type-3-diabetes/

Many people don’t realize that changing diet now may make a difference later in life. Not only in AD and the progression of the one not only the most debilitating diseases known to man but also the hardest to watch a loved one endure. It is so important for people to understand the connection between these diseases because in doing so it may aid for them to alter their lifestyle now so that they are able to experience the best possible future.

References:  

https://www.alz.org/alzheimers-dementia/10_signs

https://www.brightfocus.org/alzheimers/infographic/amyloid-plaques-and-neurofibrillary-tangles

http://www.diabetes.org/diabetes-basics/type-2/

http://www.mwhomecare.com/diabetes-alzheimers-study/

What is Alzheimer’s Disease? Most likely when you first encountered Alzheimer’s, you heard that it was an individual forgetting things that they had previously known, such as names, events, or even large portions of their lives. The first thought after that is probably: Why? How does this happen in a person’s head? There are two big things that have been found to contribute to Alzheimer’s: neurofibrillary tangles and Aβ plaques.

Neurofibrillary tangles are hyperphosphorylated aggregates of tau protein that come together as insoluble clumps due to problems caused by insulin resistance. These insoluble tangles increase toxicity in the brain and cause neurons in the brain to die. With less neurons in the brain, connections are less easily made and symptoms of Alzheimer’s start to show.

Aβ plaques are collections of amyloid beta peptide oligomers that clump together because of improper cutting of an amyloid precursor protein (APP). This improper cutting is due to a buildup of the GM3 ganglioside. This also causes the insulin receptor to be unable to receive insulin. Then insulin resistance increases.

https://healclinics.com/a-relationship-between-diabetes-and-alzheimers-disease/

Now how does this relate to Type 2 Diabetes? The answer is insulin resistance. Type 2 Diabetes is characterized as your body being unable to use insulin in the correct way. When it can’t be used, it can’t regulate our blood sugar levels causing hyperglycemia, or higher blood sugar levels than normal. We know that insulin is important in maintaining our blood sugar levels; but being a big part of the brain? That is a new idea. Insulin is made in two parts of the body: the pancreas and the brain. It is an important regulator of brain physiology and works as a cognitive enhancer. So if there is resistance to this cognitive enhancer, there will be breakdown in the brain: Alzheimer’s Disease. We see that both the neurofibrillary tangles and Aβ plaques are fundamentally involved in some way, shape, or form with insulin resistance.

http://www.drugood.com/2018/05/30/is-alzheimers-disease-called-type-iii-diabetes/

Now that we have talked a little bit about both Alzheimer’s and Type 2 Diabetes, we can see that there is a connection between the two. That connection being insulin resistance. However, it goes even deeper. Studies show that 70% of all individuals that have Type 2 Diabetes will develop Alzheimer’s Disease at a later time in their lives. That number is staggering to me and it makes me think we need to make some changes at both the individual and societal levels. Individually we need to think about what we eat and get more exercise. Since Type 2 Diabetes is largely characterized by unhealthy eating and lack of exercise, this would be the obvious place to begin. At the societal level, we need to have healthy options available as fast options, not only unhealthy options. Though much of our society is in a “go-go-go” mode, we still need to have a healthy food to fuel us through our days. Though this won’t completely fix the problem, it will likely be worth it to slow down the large numbers that are developing Type 2 Diabetes and in the future Alzheimer’s. I feel that this ‘risk’ of healthy eating and exercise is worth it to remember loved ones and large events that happen in your life.

Alzheimers is a neurodegenerative disease in individuals that are usually of an older age. One of the major components to Alzheimers disease (AD) is the role of insulin. Insulin functions in our bodies to regulate uptake of glucose for cellular processes. In neurological functions, it breaks down Aβ amyloid plaques. though if there is a lack of insulin, this results in plaque formations leading to tau plaques. These plaques result in loss of neurons, as these can prevent the proper function of the neurons.

Insulin resistance develops from an excess of GM3 gangliosides building up in the phospholipid membrane, causing dissociation of the GEM insulin receptors from the caveolae.

This lack of insulin signaling leads to a lack of glucose in individuals with type 2 diabetes, a disease that is more common in obese and overweight individuals. These diseases share many components, such as a resistance to insulin. These diseases prevalence will only become more taxing on our society, as the projected numbers for the US ranks 50% of the population to be classified as overweight or obese by 2030. This increase in the affected population will also increase the number of individuals that are at a much higher risk for AD and type 2 diabetes. The State of Obesity lists the average percentage of adults in the US is 30% in most states. With several states having 35+% of the population being considered obese. In a projected 13 years for that percentage to gradually increase to encompass more of the population.

So what can we do to prevent this?

Our lifestyle choices play a major component in the development of bad habits, which can result in becoming overweight. Once overweight, this greatly increases the risk for type 2 diabetes. Since the relationship with type 2 diabetes and AD, this also increases the chances for someone who has type 2 diabetes or is overweight to be at risk for AD.

So to take preventative measures at a younger age, as preventing one from becoming obese or overweight by being active and eating a healthy and balanced diet. As these factors become more substantial at an older age.