Cobbers on the Brain – Page 42 – Student Commentary on the Neurological Sciences

Control What We Can Control

Posted on November 5, 2020 by / 0 Comment

Our world is often dealt with unfortunate diseases that are very harmful and untreatable. Alzheimer’s is a good example of one of those particular diseases. Alzheimer’s is the number one form of dementia and is a growing disease. Through extensive research and continuation of knowledge, scientist have still not been able to come up with a treatment. Although research is in process to find a cure, there are prevention steps one can take to help their odds from preventing the disease.

Prevention of Alzheimer’s disease is not an easy task and, for some it may be impossible to achieve. However, living a healthy lifestyle can always prove to be beneficial especially when it comes to Alzheimer’s. One area of a healthy lifestyle that should be focused on is their diet. As an American, I am constantly reminded of having a better diet because implications may take place if it is unhealthy. I am guilty of not really listening to those saying this. For much of America we do not realize this until it is too late. So how does a healthy diet relate to Alzheimer’s? In class we recently discussed the correlation between Type II Diabetes and Alzheimer disease. We know that a bad diet and obesity is a main risk factor for Diabetes. To no surprise, findings also indicate Diabetes is a risk factor for Alzheimer.

When one thinks of Type II Diabetes, obesity is often a term that comes to mind. Fat cells cause inflammation which is a problem that often occurs in the brain during Alzheimer’s. Inflammation of the brain can be caused by fat cells which brings us back to our diet. We also see insulin resistance as a pre cursor for Alzheimer’s which relates identically to Diabetes. While knowing these implications, the human population continues to have increasement in obesity problems.

Seeing how Alzheimer’s may relate to our diet, we continue to put most of our focus towards a vaccine. Unfortunately, there is not enough effort put towards the controllable. We know that a bad diet can cause Inflammation. Inflammation is present in Alzheimer’s and leads to Amyloid Beta (AB) plaque formation which is ultimately the wrong in Alzheimer’s. AB formation comes from a chain of events brought upon by insulin resistance and inflammation.

As you can see inflammation is not a good thing. Although it may be unknown whether a diet would have helpedcertain indiviuduals with the formation of their Alzheimer’s, it is safe to say that it would not hurt. The world needs to start focusing on what we can control. Yes, progress is being made towards medications but why not provide more education on a healthy living. We know the harm that bad nutrition and obesity plays into our lives. Knowing this information, we still struggle to change. As the human body, we all need to become better educated within these certain controllables and then perhaps we can put a halt to the devastating disease that Alzheimers is.

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An Unlikely Pairing between The brain and Body

Posted on November 4, 2020 by / 0 Comment

What are some unlikely pairings that you have come across in your life? One that comes to my mind right away are sour cream and onion chips. These are two things individually I cannot stand on their own, but together it’s brilliant. Or I think about my teammate who was an English and Math major. These two things just simply should not go together, common sense would tell us the brain cannot be good at both those things. More surprising than either of these to me, is the connection between type 2 diabetes and Alzheimer’s disease (AD). This is a pairing, on the surface, that also seems as if it could not be. Research suggests, however, a deep connection between the two conditions exist that impacts millions around the globe.

Insulin in The Brain

When you think insulin, the first thing that generally comes to mind is blood sugar. However, Insulin also plays a significant role in brain functioning. There are specialized receptors in the brain that insulin binds to that can regulate genes, help protect the brain, facilitate neuronal grow and survival, while also assisting in neuroplasticity. Knowing what insulin does in the brain, and that there is a deficiency in Type 2 diabetes, a picture that brings the two together begins to take shape. Not enough insulin, or an inability of Insulin to bind to its receptors, means major problems within the brain. The figure below gives a nice overview of the myriad of issues that can take place, and you can see the list above is by no means exhaustive. The signaling cascades within neurons are disrupted meaning neurons do not properly develop, and they can even die. Insulin signaling also contributes to the continuation of amyloid plaques and neurofibrillary tangles that are two classic markers of AD. Furthermore, cells that die off and do not function properly, contributes to some of the typical symptoms that are seen in AD. These include the memory difficulties and confusion occurring because of cell death and the build up of plaques and tangles.

If insulin is the problem, why not just give Insulin?

Some fascinating studies have been conducted examining Insulin as a treatment for AD. These studies have shown remarkable measures of cognitive improvement after administering either a nasal or IV dose of insulin. It makes sense that if there’s not enough insulin in both type 2 diabetes and AD, giving insulin could be an effective treatment. This turns out to be the case but there is a catch. Insulin can improve cognitive functioning in patients with AD, but also can do the same for healthy, neurotypical individuals. The symptom improvement is good news, but there is little evidence that it can stop the formation of the plaques and tangles, as well as ultimately cell death. With many having Type 2 diabetes already on Insulin, it can be very difficult for researchers to piece apart what cognitive improvements can be attributed to insulin as opposed to outside causes. Like many things with AD, the data remains unclear.

Bringing it Together

The relationship between AD and type 2 diabetes is very complex to say the least. However, in both diseases’ insulin seems to be a major player. Not enough insulin, and insulin resistance means problems for both the brain and body. This unlikely coupling is perhaps one of the most important looking ahead to how we can alleviate suffering around the globe.

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A Hope For The Future

Posted on November 4, 2020 by / 0 Comment

With the continued progression of science and technology, it is becoming evident that concussions are much more common than many had thought of. Although concussions have been around for a long time, society is much more aware of them in todays day in age. An example of this is with America’s National Football League. If you were to look back into the early 2000’s, the NFL safety precautions were little not nothing. Helmet equipment was a hard piece of plastic with foam cushion in the inside. Players could lower helmets and hit with their head. Fast forwarding to today’s game, helmets are made with advanced technology allowing separation and gel-based cushion to prevent concussions. Rules are in place to discipline players who hit with their head and designated employees are in place to identify signs of concussions. Although advancements have not taken away concussions, they have made it easier to identify one.

Being able to identify a concussion is important because certain procedures need to be put in place to not make the current concussion worse. As we continue to improve the identification, we continue to lack in the treatment. Over the years, researchers have not successfully been able to treat a concussion and its future impact as a traumatic brain injury (TBI). There are multiple targets of research at the moment and one specific drug gives a promising outlook.

A neuroprotective drug, P7C3-A20, has been a hot topic in the world of traumatic brain injury. This drug was recently used in mice models that simulated TBI in middle age humans. A concussive state was put upon the mice and one year later they were given this P7C3-A20 compound. After one month of administration of this drug showed immediate affects with cognitive function. They stopped administration of the drug for some mice and checked results four months later. It showed the same results giving hope that repairment might be taking place. They continued the experiment and eventually found out that this compound was stopping chronic neurodegeneration and even showed signs of cell repairment.

An interesting aspect of this study related to a class discussion on what is going wrong in the brain. When a traumatic brain injury event occurs, our brain undergoes a calcium influx and sequestration in the mitochondria. With administration of the P7C3-A20, it was shown that cells were being protected of this calcium influx. P7C3-A20 showed increasement of proliferation in the sub granular zone of the dentate gyrus. The drug also showed to protect and repair endothelial cells. All these positive outbreaks of the compound administered have provided researchers with hope. TBI has and continues to affect much of our population and leaves a gloomy feeling when there is truly nothing, we can do about it. Within the next few years, we can expect human based trials and, researchers are confident that we could perhaps have a solution to one of the world’s unsolved mysteries.

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Unexpected and At Fault? Insulin Resistance and Alzheimer’s

Posted on November 4, 2020 by / 0 Comment

So first, what exactly is a ganglioside? A ganglioside is a complex lipid that is found in the grey matter of a human brain. These lipids are found to play a major role in brain function, and development, as well as with ‘brain remodeling’ later in a persons life. Seeing as gangliosides are important for brain activity and retention of synaptic plasticity, it only makes sense that an improper regulation of them can cause problems, and it does.

Take for example, in the development of Alzheimer’s, and β amyloid plaques. If the ganglioside GM1 becomes clustered in a plasma membrane microdomain, it can undergo a conformational change and become a binding site for these Aβ oligomers, further promoting aggregation of AβO’s into synaptoxic Aβ plaques. While that is somewhat understood for the ganglioside GM1, an accelerated degradation of the ganglioside GM2 can actually reduce the binding of Aβ on GM1, and is capable of rescuing the cognitive decline caused by GM1 and the Aβ plaques.

Interestingly enough, an unexpected enemy may be at work relating to the modulation of these gangliosides. Diabetes is shown to accelerate the development of these plaques as well as promote the accumulation of the GM1 clusters themselves and in turn, Aβ aggregates. Additionally, there are thoughts that Aβ can be the catalyst behind insulin resistance via interference in the ganglioside metabolism. This interference can cause an increase in GM3 in the plasma membrane, which fits in with another finding that high GM3 results in insulin resistance as well.

For a link between ganglioside regulation and diabetes itself at the surface level, we need to look no further than a dinner plate. A healthy diet we already know is key to not develop diabetes in many people, however it is believed that ganglioside expression in tissues is affected by deficiencies in nutrients, or in foods that do not provide ganglioside synthesis components. For example, breast milk is a very rich source of sialic acid, which happens to be a building block to a major ganglioside in terms of brain development, GM3. Infants who are not breast fed, have a much lower ganglioside content in the frontal cortex of the brain than their breast fed counterparts.

In the end, there is a dualistic relationship between these diseases, and after further research, it is clear the co-morbidity is by no means unrelated. The same plaques that are the hallmark of Alzheimer’s disease have the capability to trigger insulin resistance through both the inhibition of the IR/S to mTOR pathways, as well as via activation of the TNF-alpha receptor which leads to inflammation. On the flip side, as stated above, insulin resistance and diabetes can accelerate the accumulation of GM1 clusters, and in turn the accelerated accumulation of Aβ oligomers into Aβ plaques. The connections between these two diseases are a connection I never had expected to see, and in the future, it’s intriguing to think about how two “unrelated” diseases may be “causes” of each other in the future.

Disease/Health

How Likely Are You to Develop Alzheimer’s?

Posted on November 3, 2020 by / 0 Comment

One of the most common things you hear in relation to Alzheimer’s is “Oh all the men in my family get it, so I’m going to get it” or “It’s not in my family so I am not concerned.” The question here is how straightforward is Alzheimer’s that you can just predict it based on family history? The answer is more complex than you would think.

For a second let us only look at the APOE gene and the heritability of Alzheimer’s. The APOE gene is an apolipoprotein E protein located on chromosome 19 and is responsible for synthesizing a protein that transports cholesterol and other fat types throughout the bloodstream. This APOE gene has three types: e2, e3, and e4. Specifically, the APOE-e4 type gene is the only one that has a correlation to the development of Alzheimer’s. When you receive one copy of the -e4 gene from one parent, you are at an increased risk for developing Alzheimer’s. If you have inherited two copies of the -e4 gene, you are at an even higher risk, but not at certainty to the development of the disease. Approximately 20-30% of US individuals have one copy of the gene, whereas only 2% have two copies.

However, one thing this theory fails to consider is the penetrance of the genes, or the expression of the gene. Someone who has two copies of the -e4 gene with a low penetrance are probably at a decreased risk for developing Alzheimer’s. Many psychologists actually discourage genetic testing for this gene because most testing does not account for penetrance or other factors that would increase your risk, such as sustaining concussions or Type 2 Diabetes. Also, most commonly the inherited form of Alzheimer’s that is inherited is late-onset, so many researchers wonder what there is to stress about now if the disease won’t start showing until you are 70-80 years old.

Wait, did I just say Type 2 Diabetes increases your risk for developing Alzheimer’s? Why yes I did. One review study examined the role of insulin signaling on the development of components of Alzheimer’s, such as neuroinflammation and Ab plaques in the brain. When a receptor (TNF-a) causes inflammation in the brain it begins a cascade of insulin resistance by activating PKR which causes IRS 1 to be inhibited. When IRS 1 is inhibited, insulin is not being properly released to regulate other events, such as autophagy, synaptic plasticity, and cell cycle events. On top of TNF-a mediated inflammation, unchecked PTP1B activity initiates inflammation further and downregulates BDNF activity reducing synaptic plasticity. Deregulated mTOR signaling also is involved in retro inhibition of IRS-1 which can lead to further dysregulation of autophagy and insulin resistance. Lastly aberrant ganglioside metabolism promotes the Ab plaque aggregation and impairs insulin receptor function.

All the above information is in relation to Alzheimer’s, but all the above information is also seen to some degree in Type 2 Diabetes. Now, Type 2 Diabetes is primarily correlated to obesity and an unhealthy diet. Would eating healthy not only reduce your risk of Type 2 diabetes but also Alzheimer’s even if you have copies of the APOEe-4 gene?

Photo Sourced From: https://genesandinheritancr.wordpress.com/2011/09/20/inheriting-the-apoe-e4-gene-and-what-it-means/

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Type II and Alzheimer’s: A Vicious Cycle

Posted on November 3, 2020 by / 0 Comment

The Link

Alzheimer’s Disease (AD) is the most common form of dementia diagnosed primarily in those older than sixty five and is thought to be caused by the build up of beta amyloid creating plaques and other build ups in the brain that cause neuron degeneration and death. Although this neurodegenerative disease affects over 50 million people world wide, a cure or general treatment has yet to be found. Although, two decades ago, scientists discovered an astounding link between dementia and diabetes. More specifically, between Alzheimer’s disease and type II diabetes. Those who develop type II diabetes will have an insensitivity to insulin which can often times be treated with insulin therapy and recommended exercise, diet change, and medication. The insulin pathway can become disrupted in patients who have Alzheimer’s disease, or those who have an insulin resistance, like in type II diabetes, may develop Alzheimer’s-like symptoms that can turn into actual dementia or AD. Currently, there are four mechanisms that connect Alzheimer’s disease to type II diabetes. This includes TNF-alpha mediated inflammation, unchecked PTP1B activity, deregulated mTOR signaling, and aberrant ganglioside metabolism. Here we will be taking a deeper look into PTP1B and the role it plays in both Alzheimer’s disease and type II diabetes.

The Modulator: PTP1B

It has been recently discovered that protein tyrosine phosphatase 1B (PTP1B) is an important modulator in the insulin pathway as well as in processes in the central nervous system, processes involved in Alzheimer’s disease. In the insulin signaling pathway, PTP1B negatively regulates the insulin pathway by directly affecting the receptor or by affecting down stream substrates (IRS 1/2). It also negatively affects leptin receptors and calcium channels. Over activation of PTP1B is most commonly caused by endoplasmic reticulum stress. Here is where Alzheimer’s disease can play a role in inducing type II diabetes. If a person has AD, there is most likely amyloid plaques present in their brain. These plaques are made up of an over abundance of

Schematic shows how PTP1B over activation can intracellular processes — Schematic showing what PTP1B over activation is caused by and how it can affect intracellular processes

amyloid beta oligomers (ABOs). This over abundance can cause ER stress via neuroinflammation. So, ER stress over activates PTP1B which then goes on to over inhibit insulin signaling and receptors, leptin receptors, and calcium channels. If inhibition is present for long enough, a person can develop type II diabetes from the prevalence of insulin insensitivity, but they can also begin to develop worsened AD symptoms including synaptic plasticity and stability impairment and memory and cognition problems.

The steps described above explain how a person with AD can develop type II diabetes as well as progress the symptoms and severity of AD, but similar effects can be seen in a person who initially has insulin insensitivity. In this case, if a person develops type II diabetes from sources other than AD (unhealthy diet, overweight, environmental or genetic factors) and does not get treatment, the lack of insulin signaling can cause cognitive and memory deficits and synaptic plasticity impairment, both of which attribute to the diagnoses of Alzheimer’s disease. Then, if the symptoms become severe enough to where a person develops ABOs, the ER may become stressed increasing activation of PTP1B. No matter if a person is first diagnosed with Alzheimer’s disease or type II diabetes, it does not take much to get wrapped up into the cycle connecting the two diseases.

PTP1B Inhibition: a possible treatment?

Since PTP1B seems to be a problematic common denominator for both Alzheimer’s disease and type II diabetes patients, it seems reasonable to look here for a potential treatment for both diseases, and luckily, scientists are working on this! Inhibiting PTP1B would result in no or less inhibition of insulin signaling, leptin receptors, and calcium channels even under endoplasmic reticulum stress. This would help to decrease the chance of developing type II in AD patients as well as decrease any neurodegenerative symptoms caused by PTP1B caused inhibition. But, it has been deemed an extremely difficult task due to the fact that the active site on PTP1B that an inhibitor would attached to is shared by over 100 other “family members” of this molecule. This makes it difficult for the inhibitor to only effect PTP1B and not any other PTPs present in other parts of the body.

Fortunately, though, when PTP1B inhibitors have been administers peripherally they have been able to cross the blood brain barrier and have effects on the brain. A promising inhibitor that has been going through experimentation is that of CPT157633 and UA0713. In experimental trials these inhibitors have been shown to decrease the amount of PTP1B present in the brain. With continuous effort and research, scientists have the potential ability to create a PTP1B specific inhibitor that could help to alleviate symptoms of AD and type II diabetes or prevent one disease from triggering the other.

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Alzheimer’s: CBD as a Potential Treatment?

Posted on November 3, 2020 by / 0 Comment

Alzheimer’s is a complex disease that over time results in memory loss, confusion, and disorientation. This is why it is important to try to find either a preventative or treatment for Alzheimer’s. But in order to find a preventative or treatment, one must know what is going wrong in the brain causing this terrible disease to develop.

In The Brain

Although there are many things that are going wrong in the brain, the main cause of Alzheimer’s (AD) can be linked to one main issue: insulin resistance. Insulin resistance is the inability to produce or process insulin the way the body is supposed to. Insulin helps protect neurons, the brain’s cells that communicate with each other, and is important for learning and memory pathways. This means that insulin needs to be functioning properly in the brain, because when it’s not, there are detrimental effects. Most people think of Type 2 Diabetes (T2D) when hearing the word “insulin”. T2D is characterized by insulin resistance as well. This is ironic because T2D and AD have been linked to each other and both have common factors: inflammation and insulin resistance. There are four things that lead to insulin resistance: inflammation, too much PTP1B activity, not enough mTOR signaling, and abnormal ganglioside metabolism.

When insulin is functioning normally, it binds to insulin receptors located on the neuron. These receptors become activated and phosphorylate proteins called IRS1 and IRS2. Phosphorylation just means that phosphate molecules are put on the proteins, which then activates the proteins. These proteins then cause more activation and signaling resulting in insulin’s activities in the brain, like helping with learning and memory.

However, like stated previously, in AD the insulin signaling is interrupted. This interruption happens because of activated, malfunctioning macrophages. Macrophages play an important role in the immune system and cell death. These macrophages secrete proinflammatory cytokines, which are chemicals that cause inflammation. One important proinflammatory cytokine in AD is called TNF-α. High concentrations of TNF-α cause significant inflammation, which interrupts the insulin signaling pathway, by preventing insulin receptors from activating IRS1 and IRS2 phosphorylation. Therefore, TNF-α causes insulin resistance, ultimately affecting learning and memory.

Next, is malfunctioning PTP1B activity. PTP1B is an enzyme that regulates the insulin signaling pathway. It represses insulin normally, but when it is malfunctioning, it represses too much insulin. This happens because PTP1B dephosphorylates tyrosine residues and represses leptin. This is an issue because leptin is important for cognition and memory, as well as amyloid-beta protein plaque metabolism. This then turns off BDNF receptors causing insulin resistance and inflammation. Therefore, PTP1B just keeps dephosphorylating and turning off everything, causing insulin resistance and inflammation.

Third, deregulated mTOR signaling can cause insulin resistance. The mTOR signaling pathway regulates cell metabolism, proliferation, and survival. When mTOR signaling turns off, it also turns off insulin substrates that are no longer able to bind to their receptor. Ultimately, leading to insulin resistance. Lastly, ganglioside metabolism is malfunctioning in Alzheimer’s. The gangliosides contain a glycosphingolipid along with acids. They normally promote the accumulation of amyloid-beta protein plaques. But malfunctioning gangliosides improperly slice amyloid-beta precursor proteins (APP) which causes residues to clump together, promoting too much amyloid-beta protein plaques. Therefore, resulting in inflammation and AD.

CBD Vs. THC?

Before explaining CBD as a preventative or treatment for Alzheimer’s, it is important to note where it comes from and clear up any misconceptions that there might be about it. Cannabidiol (CBD) is a chemical found in the plant commonly known as marijuana or hemp. There are over 80 chemicals identified in this plant. One of which is the psychoactive chemical known as delta-9-tetrahydrocannabinol (THC). Like other chemicals in hemp, CBD can be extracted from hemp with little to no trace amounts of THC. Therefore, CBD does not get you high.

CBD as a Treatment?

In a study, researchers found evidence that compounds found in marijuana, including CBD, can promote the cellular removal of amyloid beta. This study showed that cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells. Although the studies were conducted on laboratory grown neurons, it still offers insight into the role of inflammation in Alzheimer’s disease. It also could provide clues to developing therapeutics for AD.

Another study had a control group and AD transgenic mice that were treated orally with CBD oil. The researchers then ran a series of tests before the cortical and hippocampal tissues in the brain were analyzed for amyloid-beta plaques, oxidative damage, cholesterol, phytosterols, and inflammation. The results showed CBD oil was able to prevent social recognition deficits and social withdrawal in mice with AD. Results also showed that CBD oil reversed cognitive deficits in mice with AD as well as provided neuroprotective, anti-oxidative, and anti-inflammatory properties. Therefore, this research provided evidence that CBD oil could potentially be used as a preventative for developing AD.

Lastly, there is evidence that CBD oil could be used to manage symptoms of AD by reducing oxygenation and inflammation, as well as stimulating and protecting the brain. CBD oil has also shown to reduce anxiety and stress that may trigger episodes of agitation and aggression in patients with AD. Though these studies have shown promising results for CBD oil being a preventative and treatment for AD. Before you take CBD oil, it is important to look at the potential side effects it may cause.

References

https://www.nature.com/articles/npjamd201612

https://content.iospress.com/articles/journal-of-alzheimers-disease/jad140921

Alzheimer’s Disease and CBD Oil: Can It Help Dementia?

Disease/Health

The Good, the Bad & the Ugly

Posted on November 2, 2020 by / 0 Comment

The Good – A snack

I recently opened the door to my refrigerator and delightfully found a tub of ice cream waiting, practically begging to-be consumed. A smile crept across my face as I pulled the tub out of the freezer for the third time that day when suddenly I remembered an article we had read in my neurochemistry course on Alzheimer’s disease and inflammation. The smile quickly faded, and the ice cream was placed back into the freezer. What does inflammation have to do with Alzheimer’s and how does that have any relevance to my third bowl of ice cream in an afternoon you may ask. I’m here to tell you, more than you think.

The Bad – Alzheimer’s

Alzheimer’s disease is a neurodegenerative condition characterized by loss of memory and other important mental capacities. These malfunctions occur as a result of decreased brain cell connections due to neuronal cell death. Neurons contain a diverse array of cellular machinery and proteins significant to their health and proper functioning. Two of the primary issues in Alzheimer’s are neurofibrillary tangles and beta-amyloid plaques. These result due to issues with the proteins tau and beta-peptide oligomers both of which accumulate and coagulate resulting in neuron and tissue death. The tissues die because coagulation of these proteins blocks the movement of materials inside the cells and the transmission of signals outside and amongst the cells leading to a total loss of function and degeneration of the neurons. But how does that relate to inflammation?

The Ugly – Inflammation

Inflammation specifically chronic low-grade inflammation of tissues recruits cells from the immune system called macrophages (in the body) and microglia (in the brain). This inflammation results in increased activity of a protein abbreviated as PTP1B which has the role of dephosphorylating (deactivating in most cases but not all) other proteins and signaling pathways. This deactivation of important proteins such as IRS1 & IRS2 prevents them from enacting their functions of blocking the over activation of another protein abbreviated as mTOR. When mTOR signaling is improperly regulated then beta-peptide oligomers and tau turn into neurofibrillary tangles and beta-amyloid plaques which develop through a continued long and complex scheme of further improper signaling. MTOR malfunction also leads to insulin resistance which is at the sole of Alzheimer’s disease and its development.

– Insulin Resistance

Insulin is a hormone produced in the pancreas (and brain in small quantities) that plays several important roles both within the body and within the brain. Within the body, insulin regulates the metabolism of carbohydrates, fats, and proteins by promoting the absorption of glucose from the blood. Its resistance is the primary cause of type 2 diabetes. Within the brain, insulin plays a neuroprotective role, regulates synaptic plasticity, long-term memory consolidation, and participates in regulating neuron growth and survival. Insulin resistance within the brain leads to neuron vulnerability, degeneration, and Alzheimer’s disease. Because of insulins diverse and significant roles, having type 2 diabetes puts one at risk for developing Alzheimer’s disease and vice versa.

The Ice Cream

Okay that all makes sense (inflammation leads to beta-amyloid plaques, neurofibrillary tangles, and insulin resistance which causes Alzheimer’s disease) but what relevance does ice cream have? A healthy diet is important and can have a positive impact on the prevention of developing multiple conditions including Alzheimer’s disease and type 2 diabetes. A poorly balanced diet, especially one high in fat can stimulate the body to increase its fat stores. It’s this increase in fat storage that recruits immune cells resulting in inflammation and initiating the cascade of events leading to said conditions. Of course, eating ice cream responsibly is of no concern and certainly won’t lead to the development of type 2 diabetes or Alzheimer’s disease in the average individual, but a consistent pattern of poor diet and numerous other factors such as lack of exercise could contribute to an increased risk of development. There remains much to learn about the link between insulin resistance, type 2 diabetes, and Alzheimer’s disease including Alzheimer’s cause and possible treatment strategies. But, with the knowledge we do have, we can be proactive in an effort to best protect ourselves and those we love. Thanks for reading.

Sources

https://pubmed.ncbi.nlm.nih.gov/29129775/

https://www.google.com/search?rlz=1C5CHFA_enUS867US867&ei=3w6fX6j-F8Sf_Qby65G4DA&q=insulin&oq=insulin&gs_lcp=CgZwc3ktYWIQAzIHCAAQyQMQQzIECAAQQzIHCAAQsQMQQzIECAAQQzIHCAAQsQMQQzIFCAAQsQMyBQgAELEDMgQIABBDMgUIABCxAzIFCAAQsQM6CAgAELEDEIMBOgIIADoLCC4QsQMQxwEQowI6CAguEMcBEK8BOgoIABCxAxDJAxBDOgoILhCxAxCDARBDUJ3uzQFYpvjNAWDF-80BaAFwAXgAgAGpAogBlwiSAQUwLjYuMZgBAKABAaoBB2d3cy13aXqwAQDAAQE&sclient=psy-ab&ved=0ahUKEwjo6cDFjOLsAhXET98KHfJ1BMcQ4dUDCA0&uact=5

https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/symptoms-causes/syc-20350447?utm_source=Google&utm_medium=abstract&utm_content=Alzheimers-disease&utm_campaign=Knowledge-panel

Disease/Health

Alzheimer’s: More Risky Than You Think

Posted on November 2, 2020 by / 0 Comment

Alzheimer’s: the complicated disease resulting in memory loss, confusion, and disorientation. Odds are we’ve all heard of this disease and the profound implications it can have on people’s lives, but there may be much more to this issue than we have previously understood.

In the brain:

In Alzheimer’s, there are obviously many things going wrong in the brain, leading to the complex nature of the disease. However, the cause of Alzheimer’s can really be boiled down to one main issue: insulin resistance. Insulin is crucial to the brain’s normal functioning, so issues with it working properly have detrimental results. There are essentially four facets that lead to the insulin resistance seen in Alzheimer’s. These are: inflammation, unchecked PTP1B activity, deregulated mTOR signaling, and abnormal ganglioside metabolism.

The first part of the insulin resistance understanding of Alzheimer’s is inflammation. Inflammation in the brain is known to cause insulin resistance, considering it impairs synaptic functioning and goes hand-in-hand with stress on the endoplasmic reticulum. Next is unchecked PTP1B activity. PTP1B is an enzyme that is an important regulator of the insulin signaling pathway. It is a negative regulator, which is important when working properly, but when unchecked, causes insulin resistance. The third facet of insulin resistance comes from deregulated mTOR signaling. The mTOR signaling pathway is an important regulator of cell metabolism, proliferation, and survival. When mTOR signaling is off, it retroactively inhibits insulin substrates so that they are no longer able to bind to their receptor. This once again leads to the insulin resistance seen in Alzheimer’s. Finally, ganglioside metabolism is abnormal in Alzheimer’s. These gangliosides, specific molecules containing a glycosphingolipid and one or more acids, promote the aggregation of amyloid-beta protein plaques that run wild in Alzheimer’s.

With all of the previous implications considered, we can see that insulin resistance is an important contributor to Alzheimer’s and may be a significant system to target when thinking about future treatments and therapies. What’s also quite fascinating is that all four of those causes are also linked to the insulin resistance seen in type 2 diabetes. Many of us likely did not know that type 2 diabetes and Alzheimer’s are so interconnected in causes and mechanisms. Here is a figure that summarizes these concepts:

Image source: Vieira MNN, Lima-Filho RAS, De Felice FG. Connecting Alzheimer’s disease to diabetes: Underlying mechanisms and potential therapeutic targets. Neuropharmacology. 2018 Jul 1;136(Pt B):160-171. doi: 10.1016/j.neuropharm.2017.11.014. Epub 2017 Nov 10. PMID: 29129775.

Outside the brain:

Now that we’ve taken a look at what exactly is contributing to Alzheimer’s within the brain, it’s also important to keep in mind the factors that come from outside the brain and body: from the environment.

The most important risk factor for Alzheimer’s is increasing age (which many of us might have guessed!) but other environmental risk factors are not well understood, though they are quite prevalent. One study suggests that half of the individual differences seen in Alzheimer’s risk levels may be environmental. In other words, half of any one person’s chances to develop this disease could be attributed to environmental causes, which is insane! Obviously with findings this significant, there needs to be a better understanding of environmental factors in Alzheimer’s. It is crucial to understand the full Alzheimer’s exposome, which is another word for the complex gene-environment interactions that lead to individuals’ higher or lower susceptibility and onset of Alzheimer’s.

There are several environmental factors known to have a role in Alzheimer’s risk. Some main ones are exercise, traumatic brain injury, blood pressure, smoking, education, and air pollution. Interestingly, researchers have found that the onset of dementia was a decade earlier in individuals with these environmental risks. A whole decade! Obviously with environmental factors having this significant of a shift in the onset curve, we must begin to think about how our lifestyle shapes our life outcome.

We now see that Alzheimer’s is much more complex than originally understood. Considering insulin resistance, environmental factors, and link to type 2 diabetes, this disease deserves much more recognition and research so we can hopefully work towards a better understanding, and eventually, a cure.

Disease/Health

Estrogen, Insulin Resistance, and Alzheimer’s Disease: A Love Triangle

Posted on October 31, 2020 by / 0 Comment

Insulin Resistance and Alzheimer’s Disease:

The first two members involved in this complicated love triangle are insulin resistance and Alzheimer’s Disease. There is a remarkable link between the two, as insulin resistance increases the likelihood that an individual develops Alzheimer’s Disease, and vice versa. This connection between these two conditions are the result of a variety of overlapping mechanisms at the cellular level that contribute to the development of one or both ailments.

Insulin has numerous beneficial effects throughout the brain including protection for neurons, growth and survival of neurons, and reinforce neuroplasticity, a mechanism that allows for long-term memory consolidation and maintenance. When there is a deficiency in insulin as a result of insulin resistance, these neuroprotective effects are absent and put the brain at higher susceptibility to developing Alzheimer’s Disease.

Estrogen and Insulin Resistance:

The other member in this love triangle is the reproductive hormone, estrogen, that prepares the lining of the uterus for pregnancy, along with a number of body-wide effects. Low levels of estrogen have been linked to insulin resistance in numerous studies, suggesting a prominent role of estrogen in maintaining normal insulin signaling. This deficiency in estrogen that leads to insulin resistance that, as mentioned above, can put an individual at a greater risk of developing Alzheimer’s Disease.

Estrogen and Alzheimer’s Disease:

Decreased levels of estrogen can also directly increase the likelihood of the development of Alzheimer’s Disease, in addition to the role of estrogen in insulin resistance, as demonstrated above. This effect can be seen in the form of estrogen as a neuroprotective agent in the brain. In particular, estrogen helps to prevent the synthesis and accumulation of beta-amyloid (Aß) plaques. These plaques have neurotoxic effects within the brain, as the presence and buildup of these molecules have shown to be a primary root cause of Alzheimer’s Disease.

Clinical Applications:

Menopause is categorized by decreased estrogen levels as those who menstruate age. This stage of reproductive health therefore leads to an increased risk of developing insulin resistance and eventual Alzheimer’s Disease as a result of estrogen deficiency.

Since low estrogen has indeed been linked to insulin resistance, this is largely why post-menopausal women tend to gain weight and have a greater likelihood of developing Type 2 Diabetes. Additionally, menopause as a result of surgical hysterectomies, in which the ovaries are also removed, results in two times greater likelihood of developing Alzheimer’s disease in those who underwent the procedure than those who did not. This increased risk is largely associated with a loss of estrogen. These clinical commonalities further emphasize the role of estrogen in the protection against both insulin resistance, and ultimately, Alzheimer’s Disease.

Estrogen as a Potential Treatment Option

Estrogen is one of the best-studied drugs for potential use in the prevention and/or treatment of Alzheimer’s disease. Estrogen therapy can reduce the cognitive decline observed in women that have gone through either natural or surgical menopause. This form of therapy can therefore help to delay or be used in the treatment of both Alzheimer’s Disease and Type 2 Diabetes. Supplemental estrogen also improves the function of Tacrine, an anticholinesterase drug that is used for the treatment of Alzheimer’s Disease, thus demonstrating that estrogen may enhance existing treatments for Alzheimer’s Disease. Further research regarding the therapeutic effects of estrogen should be pursued, as its positive effects in preventative measures against insulin resistance and Alzheimer’s Disease are invaluable in the fight against these health issues.

Abstract (Featured Image) created by S. Wiger