Cobbers on the Brain

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.

Linking Alzheimer’s Disease and Type II Diabetes

The Link

When picturing an individual suffering from Alzheimer’s disease (AD) and one suffering from Type II Diabetes (T2D), these pictures look greatly different. However, zooming in past the physical symptoms and appearances, we can look closely at the specific ways these disorders work. Tied together by the mechanisms of neuroinflammation, insulin resistance, and ganglioside function, AD and T2D are more similar than we might imagine.

Image 1: The biological connections in grey can be studied between AD and T2D and represent the two-way street these disorders pave in our brains.

What is Insulin?

Insulin is a hormone generally made in the pancreas that helps our body take in glucose, which is processed and used for energy and stored in our cells for future use. In diabetes, this process does not function. In type II diabetics, insulin is produced but not able to complete the signaling pathway to intake glucose.

The Pathway:

Insulin leads to the uptake of glucose through the pathway represented in the above image. Insulin binds to the transmembrane insulin receptor (IR). This activates the IRS1, leading to a phosphorylation cascade ending with the translocation of GLUT receptors to lipid rafts (compartmentalized sections) in the membrane.

Understanding Alzheimer’s:

Alzheimer’s disease is characterized by the buildup of amyloid plaques and neurofibrillary tangles in the brain. The pathway to these malformations is complex, but has many connections to neuroinflammation and insulin resistance.

Connecting the Pieces

The pathways of AD and T2D connect through insulin resistance and neuroinflammation. The two figures below detail the complex mechanical connections between the diseases. More specific information on these topics can be found at source links 1 and 2 below.

Image 3: Insulin resistance affects the production of glucose peripherally. This dysfunction in the CNS contributes to the formation of amyloid beta plaques and neurofibrillary tangles in the brain.

Image 4: This pathway shows that many factors (ex: PKR, S6K, PTP18, GM3) directly inhibit the processing of insulin. The buildup of GM3 molecules physically disassociates the IR from its connection with IRS 1/2, causing reception to be halted. The GD3 molecules that are made from GM3 perpetuate the buildup of Amyloid Beta plaques, showcasing the connection to AD.

So what?

Using the connections in mechanism between T2D and AD can inform future treatment options and research in both conditions. Seeing the parallel nature in pathophysiology between the conditions, it isn’t surprising how often the two disorders overlap. The knowledge gained from a dual-perspective view at both AD and T2D can influence further research in not only these conditions, but also other neurodegenerative conditions involving neuroinflammation due to the buildup of malformed molecules in the brain. This research has the potential to impact a large community of individuals and family members who are affected by neurodegenerative diseases or Type II Diabetes.

Sources for further research

• https://www.researchgate.net/figure/Schematic-diagram-of-the-insulin-signaling-pathway-Binding-of-insulin-to-the-a-subunit_fig2_232231667
• http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1980-57642017000200105
• https://www.abcam.com/pathways/overview-of-insulin-signaling-pathways
• http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1980-57642017000200105
• https://www.google.com/search?biw=1241&bih=715&tbm=isch&sa=1&ei=WRa8W6OxPO-l_QbNw6-ICA&q=alzheimers+and+diabetes&oq=alzheimers+and+diabetes&gs_l=img.3..0i10i24.15202.17476..17593…1.0..0.297.2054.4j5j4……1….1..gws-wiz-img…….0j0i10.cMHLL_jyY7Y#imgrc=67SBnaVcq0xlOM:

The Concordia College Neuroscience Program aims to consider and connect as many interdisciplinary perspectives as possible. As students, we are taught to think critically and connect our experiences to the curriculum. This perspective helps in discussing the possible causes and connections in neurodegenerative diseases. When discussing Alzheimer’s Disease this week, the class considered the similar pathways and concepts we learned last week with Autism Spectrum Disorder (ASD). Students also considered their personal connections and experiences with neurodegenerative diseases.

Although we have all learned about Alzheimer’s Disease in our courses, many of us also have personal connections to the neurodegenerative disease. According to the 2018 facts and figures released by the Alzheimer’s Association, 5.7 million Americans currently live with Alzheimer’s Disease. The number of deaths related to Alzheimer’s Disease has increased by 123% from 2000-2015. The association notes that every 65 seconds, another individual develops Alzheimer’s Disease in the United States. Cases of dementia, including Alzheimer’s Disease, are responsible for the death of 1 in 3 senior Americans–this is more than Breast Cancer or Prostate Cancer combined.

Like a few of the other students in the class, I have a familial connection to Alzheimer’s Disease. Due to many members within the older generation of my family developing Alzheimer’s Disease, I fear that I too may develop the disease in the later years of my life. We know from previous research that there is a hereditary factor linked to Alzheimer’s Disease. Previous research has shown that mutations in genes APP, PSEN1, and PSEN2 have linkages to early onset Alzheimer’s. Likewise, research on late-onset Alzheimer’s Disease found 20 different genetic loci associated with the disease. Specifically, APOE4 is a gene correlated with the familial development of Alzheimer’s Disease–one that shows the heritability of the disease. Regardless of the heritability and genetic factors of dementia, previous research has also shown the importance of the environmental factors associated with the development of the disease–and in many cases, the genetic and environmental factors both contribute to the development of Alzheimer’s Disease. Paying attention to these environmental factors may decrease my chances of developing this neurodegenerative disease.

These environmental factors include:

• Diet
  • Type 2 Diabetes has been linked to Alzheimer’s
  • The insulin resistance leading to Type 2 Diabetes likely stems from a fatty diet
  • Other popular media articles have discussed how red meat might lead to Alzheimer’s
  • The prevalence of Alzheimer’s Disease in the United States more than likely is due to our diet and lack of exercise.
• Exposure to toxic chemicals
• Serious brain injury
• Air pollution

When discussing Alzheimer’s Disease and many other neurodegenerative diseases, it remains important to note the vital interaction between genetic and environmental factors resulting in the development of disease. With the prevalence of genetic testing in today’s society, specifically through companies like 23andMe, people can know in approximately 6-8 weeks if they possess some of the genes associated with Alzheimer’s Disease. Without proper consideration or education, members of society may be mislead to think that they are destined to develop the disease. That may not be the case. It is more likely that even if an individual possesses the gene associated with a disease, environmental factors play a large role in whether or not that gene is transcribed or “turned on.” Research has shown that paying attention to the environmental risk factors above, and changing lifestyles to match, may reduce a person’s risk for Alzheimer’s Disease.

https://moodle.cord.edu/pluginfile.php/723477/mod_resource/content/0/2018%20AD%20and%20insulin%20signaling.pdf

https://www.alz.org/media/HomeOffice/Facts%20and%20Figures/facts-and-figures.pdf