Cobbers on the Brain – Page 126 – Student Commentary on the Neurological Sciences

Novel Brain Scan Technique Could Definitively Diagnose Alzheimer's Disease

Posted on March 2, 2016 by / 0 Comment

What is Alzheimer’s Disease?
Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that destroys ones memory and many other important mental functions. At a basic level these symptoms are caused by a dysfunction of neurons and the communication of neurons, the synapses. For many years two defining characteristics of AD found in postmortem brains of AD patients were neurofibrillary tangles and amyloid plaques. These two very “sciency” words essentially mean large accumulations of certain types of proteins that cannot get broken down. Along with the tangles and plaques, recent studies have shown a correlation between AD and type 2 diabetes. It seems that in people with AD the insulin signaling pathway in the brain, yes insulin does play a role in the brain, is damaged. The insulin pathway in the brain has been shown to play a key role in our learning and memory. In people with type 2 diabetes their insulin receptors are resistant to insulin. In other words people with type 2 diabetes do not have a problem producing insulin, like people with type 1 diabetes, but their body simply does not respond the way it should to insulin. Researchers believe that insulin resistance is one of the causes of the symptoms seen in AD.
How do we Diagnose Alzheimer’s now?
According to the Mayo Clinic the current action for diagnosing AD is to perform memory and impairment tests, look for behavior changes, look at medical history and rule out other ailments that could be causing these symptoms. Once all of this is done then a doctor may diagnose a person with AD. With that said the only sure fire way to correctly diagnose a person with AD is by looking at the brain postmortem.
Can we diagnose AD with more certainty and earlier?
Recent research at two Canadian universities may have found a way to achieve an earlier and more definitive diagnosis. By studying postmortem brains of patients with AD the researchers discovered an enzyme that gathers around the plaques and tangles characteristically found in AD brains. Not only does this enzyme gather around AD specific plaques and tangles but it seems to stay away from other similar plaques. Using this knowledge researchers were able to develop a small radio-labeled molecule that can bind specifically to these plaques and tangles. The important part about this radio-labeled molecule is that is can show up on PET scans of the brain. Currently there are still some obstacles before this type of diagnosis can be used on for AD patients. For one the radio-labeled molecule has yet to used on humans and the diagnosis would be very expensive.

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Alzheimer's Disease: A Disease Worth the Research

Posted on March 2, 2016 by / 0 Comment

There is no getting around it – Alzheimer’s Disease is devastating. It affects the lives of not only those afflicted, but also their families and friends. And it’s not even one of those things that just weighs on the minds of those involved; it often becomes the center point in familial dynamics. Many times having a family member diagnosed with AD comes with months and years of assistance, planning for the future, and constant stress and worry. And this is for good reason – the disease affects the memory, thinking, and behavior of the patient, with the symptoms worsening over time. But recently, I have heard points being made that an AD diagnosis could possibly be something everyone experiences, whether they live long enough to develop it or not. Before discussing that, however, it’s important to understand what exactly goes wrong in the brains of AD patients.

Although the exact cause of AD has been extensively researched, it is still largely un known. What has been examined is the connection to a faulty breakdown of amyloid precursor protein, or APP. APP is a single-pass transmembrane protein expressed at high levels in the brain that’s broken down into the AB oligomer (ABO) AB-40 by various enzymes. In a normal brain, APP is broken down into AB-42, a slightly larger ABO, about 5% of the time. . At low levels like this, AB-42 is cleared easily by the natural systems in the brain. However, in the brains of AD patients, APP is broken down into AB-42 about 40% of the time, which results in much higher levels of the larger oligomer. At these high concentrations, it begins to aggregate, which leads to the activation of the microglia in the brain. These microglia then destroy and remove cells in an attempt to clear the large AB-42 aggregations. This leads to neurodegeneration – a major factor in AD. Now, there are various other abnormal processes occurring in the brains of AD patients, but it is thought that the aggregation of large ABO’s in the brain could be the most significant.

So, does this eventually happen in everyone’s brain? Does everyone eventually begin to have AB-42 build up, microglia activation, subsequent neurodegeneration, and eventual memory loss and cognitive decline? Current research wo uld suggest that the answer is no; however, I think it’s interesting to explore the possibility that the answer is actually yes. What if this process started with some people at an earlier age than others, or for some it doesn’t start until they would hypothetically turn 110 years old?

It’s a scary thought, that’s for sure. But it also raises a controversial question: should we continue funding AD research if everyone eventually gets it? Is there even a point? One side may say that the amount of money put into AD research is too high, and that even if we did find a “cure” for the disease, a different one would eventually take its place. Another side focuses on the severity of AD itself, how many people it affects, and how AD needs to be further studied. I, personally, take the second side. I think of the multitude of individuals and families that are affected by the specific effects of AD – memory loss and cognitive decline. Although I personally haven’t been affected by the disease, I cannot begin to imagine the toll it must take on those who have. To those backing the side that suggests researching AD is a waste, I can’t help but ask if there could possibly be a worse disease to take the place of AD. But, like many subjects in neuroscience, no clear-cut answer can be determined today. Therefore, the many scientists devoting their lives to trying to understand this disease should continue with their efforts, it is worth the research.

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Could Diabetes lead to Alzheimer's Disease?

Posted on March 1, 2016 by / 0 Comment

In the world of medicine, Alzheimer’s Disease (AD) a hot topic in the recent decades. With it affecting over 90,000 Americans annually, the prevalence of this disease is on the rise. While a majority of research has focused on possible cures or reversing the degenerative affects of this disease, recent studies have taking a different approach to tackling this topic. Rather than concentrating efforts to fix or cure the degenerative effects of Alzheimer’s, researchers have begun to look into preventative care methods and causal mechanisms for this disease. One such correlational condition to Alzheimer’s is type II diabetes.
Characterized by insulin resistance, type II diabetes, also known as adult-onset diabetes, is a disease in which the body is unreceptive to insulin leading to higher concentrations of glucose in the blood. It has also been shown to disrupt many of the neurological pathways leading to development of Alzheimer’s. Insulin has been shown to regulate brain metabolism and energy balance in the hypothalamus along with stimulating memory formation, association, and retrieval in the hippocampus and forebrain. The binding of insulin also plays a major role in cognitive functioning and has been linked to many neuroprotective properties.
Most commonly, patients with Alzheimer’s display two distinct neurological characteristics: senile plaques and neurological tangles. Large clumps of amyloid fibrils (amyloid-beta peptides) are what make up senile plaques. While the aggregation of these peptides chains has shown to be toxic, recent studies have proven that this is not the leading cause of Alzheimer’s symptoms. Rather, it has been cited that the loss of plasticity or neuronal signaling that has been most strongly associated with Alzheimer’s like symptoms and is correlated with the formation of oligomers of Alpha-beta peptides called, Alpha-beta oligomers. These toxins have now been considered responsible for the synaptic loss that encompasses Alzheimer’s disease.

Without the ability for the body to be receptive to insulin, the brain is not able to function properly and can lead to the neurological tangles and plaque build ups as previously described. Because of this, it is essential when discussing preventative care methods to include a healthy diet. This may be the number one preventative care treatment as a healthy diet, along with exercise, significantly decreases the chances of developing type II diabetes. It is important to note that individuals with type I diabetes are not as high of a risk of developing AD since their symptoms can be treated with an insulin agonist. This is because patients with type I diabetes are not resistant to insulin, instead their bodies are not able to naturally produce insulin. Therefore, when given an artificial insulin supplement, the body will function properly.

As a society, if we do not seek to improve our diets, not only will our immediate lives be altered, but the long-term conditions of our lives could be severely compromised. While it may appear that this may just be a biological issue in the science community, if we wish to truly improve the lives of people around the world and in our nation, we must view this as an economic issue as well. Healthy food needs to be more accessible for everyone or else there will be a substantially larger population of people living in high needs nursing homes, contributing to the national economic deficit.

Disease

Connecting Alzheimer's Disease with Insulin Signaling in the CNS

Posted on March 1, 2016 by / 0 Comment

Alzheimer’s Disease (AD) is a disastrous neurological degenerative disease that effects more and more people each year. Cures and treatments for AD have been minimal at best and until recently didn’t show much promise. It was originally thought that the build up of amyloid beta plaques start overwhelming portions of the brain and eventually kill neurons, however, a recent study found that the removal of these plaques from the brain didn’t show in improvement of cognitive functioning in the patients. What instead was found was accumulated amyloid beta oligomers (AβO) causing a synaptotoxin effect.
A new direction of research was observed. The role of insulin in the brain. Until recent years the brain was considered an “insulin-insensitive organ”, but recent research has shown the central nervous system to rely on many insulin actions for potential neuronal survival and other important functions.
Insulin, from the pancreas, travels through the blood stream to the blood brain barrier (BBB) where it crosses and enters the CNS. Here it is known insulin helps regulate brain metabolism by acting on the hypothalamus. Insulin acts on insulin receptors (IR) which are found in various forebrain areas important for memory formation, consolidation, and retrieval. Clearly, insulin signaling is important in memory functioning, and AD has memory disfunction as a primary symptom.
Another recent study found that a build up of AβOs in various areas in the brain could potentially result in a disfunction of IR in neuronal membranes by pushing the IRs intracellular deeming them useless. This would result in a direct cognitive disfunction in whichever area in the brain the IR is associated with, for instance in the hippocampal forebrain would cause memory impairments.
This connection between AD and insulin signaling in the brain opens up a new door for research. It is possible new treatments for AD could arise from the new research of the insulin pathways in the forebrain. Unraveling these mysteries could could reveal powerful therapeutic opportunities for this devastating disease.
Citation:

Easing the anguish of Alzheimer’s disease

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Alzheimer's and Diabetes: The Link We've Been Missing

Posted on March 1, 2016 by / 0 Comment

Until recently the brain was thought to be a insulin-insensitive organ. It has been discovered that there are various actions of insulin in the brain. Insulin acts on the hypothalamus to control brain metabolism and body energy balance. Insulin signaling also plays an important role in all aspects of memory. It is required for synaptic plasticity and learning.
Amyloid plaques are a key trait of Alzheimer’s and for a long time was thought to be the reason for memory loss. After examining brains post mortem there is no correlation between the amyloid plaques and memory loss. The cognitive decline was found to be connected to synapse damage.
Alzheimer’s and diabetes have very similar pathophysiological and clinical traits. Brains with Alzheimer’s disease have defective insulin signaling which leads to synaptic dysfunction and memory issues.
There is currently research being done to discover if the mechanisms that underly impaired peripheral insulin signaling in type 2 diabetes and alzheimer’s are related.
So what does this mean? This means that there may be a direct link between the underlying mechanisms of type 2 diabetes and Alzheimer’s. The current mechanism of Alzheimer’s is pretty unclear. It cannot be diagnosed until after death and because of that it is even more difficult to study.
Now we see that having a healthy lifestyle may not only save you from type 2 diabetes but also Alzheimer’s disease.

That might not be enough for some people, fortunately diabetes are a well researched and treated field. It is difficult to treat Alzheimer’s, because we don’t understand the mechanism. Finding this connection could lead to some treatment choices after the damage has begun. Using anti diabetic treatments for patients with memory loss could be on the horizon.

Disease/Health/Hot topics

Diabetes and Alzheimer's: a relationship few have thought about.

Posted on March 1, 2016 by / 0 Comment

The topic for this week in Neurochemistry, the class of wonderful authors featured on Cobbers on the Brain, was a topic that hits home for millions of people around the world: Alzheimer’s disease. Having never done extensive research on the topic, I was very curious to know how and why this devastating disease developed, but just like almost all neurological diseases, the possibilities seemed to be endless. The article we discussed explained the possible connection between diabetes and Alzheimer’s development. More specifically, it looked at insulin resistance that characterizes type 2 diabetes and its role in the disease.

For both Alzheimer’s disease and diabetes, altered cell metabolism, inflammation, and insulin resistance are key pathological features in both diseases so this led researchers to explore a possible relationship between the two. It is also well known that insulin plays a role in the regulation of Beta-amyloid, the protein that builds up to form plaques in patients with Alzheimer’s. Insulin receptors have also been found to be key component in memory formation and have been found to be compromised in early stages of Alzheimer’s disease. All of these relationships direct a bulk of current research to the thought that insulin resistance, like seen in diabetes, could be directly related to the development of Alzheimer’s later in life.

What do these findings mean for Americans today?

For our society with increasing rates of obesity and diabetes, these findings should be alarming. The relationship between insulin resistance and Alzheimer’s could mean that as America continues to become a population with high rates of diabetes, more and more people could be at greater risk for developing Alzheimer’s disease.

(#artstracts)

On a positive note, this research has opened doors to the possibility that insulin resistance treatment in the brain could eventually be a treatment for Alzheimer’s disease. If it could be determined how to overcome the insulin resistance in Alzheimer’s patient brains, then the development of amyloid plaques could be reduced and memory function increased.

As research continues on this topic, I think it’s important to recognize that our lifestyle choices today always have the potential to greatly impact our future. If the thought of obesity and diabetes isn’t scary enough, always try and remember to think about that precious brain of yours!

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The Rise of a New Era?

Posted on March 1, 2016 by / 0 Comment

Will the older generations begin to look different with the rise in type II diabetes? Recently more and more studies have been shown to prove that having type II diabetes greatly increases the risk of developing Alzheimer’s disease.
The way our society has been eating and the lack of exercise as a whole has contributed to an exponential growth in the amount of individuals who now have diabetes. With this being known, will the baby boomer generation cause an increase in the number of Alzheimer’s disease patients?
In Alzheimer’s disease brains, large plaques of amyloid-beta oligomers (ABO’s) are found and is thought to be one of the main components in cognitive impairment. The initiation of Alzheimer’s disease is still unknown but is thought to be caused by a various collection of impairments, such as endoplasmic reticulum (ER) stress, malfunctioning insulin signaling, and inflammation.
Another large factor in the progression of Alzheimer’s disease is the loss of insulin receptors in the brain. Insulin is produced in the pancreas and travels through the blood. Once near the brain, it crosses the blood brain barrier. When, for example, someone has insulin resistance, insulin is not properly being used and the brain is then affected.
Receptors are continually being recycled into the cell through clathrin-coated pits and replaced for maintaining the cell membrane. But in Alzheimer’s disease, insulin receptors are not being replenished back into the membrane, inhibiting the amount of insulin that needs to bind and then enter the cell. Insulin begins to accumulate in the synaptic cleft, and this is where research is still unclear but is thought to cause a cascade of events that ultimately leads to neuronal death and memory loss.
With all that we know about the relationship between insulin resistance in type II diabetes and Alzheimer’s disease, our society should begin thinking about the potential rise in Alzheimer’s disease patients throughout the United States.
Questions arise like, how we will take care of these individuals and whether or not we should be putting more money into researching a cure so that it can be prevented as much as possible. With no concrete future direction it is up to us to inform others and begin taking better care of our bodies.

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Diabetes and Alzheimer’s: Eating Healthy Results in More Than Just Weight Loss

Posted on March 1, 2016 by / 0 Comment

In Neurochemistry class, we talked about Alzheimer’s Disease, which is one of the most detrimental disorders that someone can experience. We talked about how there are a lot of different theories for the etiology of the disorder (i.e. genetics) and other associated factors.
We learned about Amyloid-Beta plaques and oligomers, which are basically just strands of misfolded/dysfunctional proteins that disrupt neuron signaling, eventually leading to cell death and, moreover, cognitive decline.

One of the most interesting things that I learned, however, was the association between Alzheimer’s Disorder and Type II Diabetes. Current research is explaining how LDL, or “bad cholesterol,” is linked with Alzheimer’s in that it can lead to the increase in AB build-up in the brain which, as mentioned before, is also concomitant with AD.
In a review done in 2013, they mentioned multiple studies that have linked Type II Diabetes to Alzhiemer’s, and how that association has increased substantially in the last few years. It is estimated that it is because of the Westernized lifestyle of high-caloric food intake with a lack of exercise.
The study also mentioned how they have found that both AD and Type II Diabetes have insulin resistance, which results in an increased amount of blood sugar and, therefore, a higher potential for AB plaques and cell death.
Insulin plays a very important role in metabolism and protein synthesis. Basically, we need this hormone to form memories and process our food. Without it, we would experience cognitive impairments such as memory loss.
Current research is showing promise for insulin treatment and the slowing of Alzheimer’s symptomology, although more research is needed to confirm this hypothesis.

The take-home message that I absorbed through our last Neurochemistry class was that eating healthy and exercising does more than just help you lose weight. There is a substantial amount of supporting evidence that eating right and working out can lead to less “bad cholesterol” build-up, and decrease your risk for Type II Diabetes and, therefore, potentially decreasing your risk for Alzheimer’s disease.
Again, more research is needed to fully understand how to fully prevent this order, but I now know to eat more apples and walk to class more than I currently do.

Disease

Good News for Meredith Grey? An Investigation into the Mechanisms of Alzheimer’s Disease

Posted on March 1, 2016 by / 0 Comment

For all of the Grey’s Anatomy fans out there, in season 9 we discover that Meredith does in fact carry the gene for Alzheimer’s—inherited from her mother. The discovery is dire.
And while we were reassured by McDreamy’s consoling of Meredith—in that genes don’t determine our fates—the fact of the matter is Meredith is at risk for this detrimental disease.
It is also likely that an increasing number of our population is at risk. In this week’s research, our class found links to insulin intolerance and the development of Alzheimer’s Disease (AD).
With type II diabetes diagnoses on the rise, this increased insulin intolerance could lead to a rise in Alzheimer’s Disease diagnoses in the coming years.
This makes the study of AD imperative, and the search for treatments, as well as preventative measures all the more a priority.
The good news? Our understanding of the chemical underpinnings of the disease are increasing, and the research we have delved into seems to suggest we might be on the brink of finding the true root of the problem.
The Importance of Insulin
Recent research has shown the importance of insulin in the brain. Insulin naturally crosses the blood brain barrier and regulates many important functions in neurons.
When a person experiences insulin resistance, this could result in less of the vital insulin signaling functions in the brain, leading to memory impairment and AD development.
Decreased insulin signaling also leads to increased tau phosphorylation. Tau is an enzyme in the brain that’s normal functioning is important for microtubule structure in axons of neurons. When phosphorylated, tau’s actions are inhibited—thus creating issues with axon signaling.
Phosphorylated tau protein combines and aggregates into plaques or neurofibrillary tangles (NFTs). These NFTs have been major signs of AD for many years and were originally thought to be the cause of AD.

Thus, the new found link between tau and insulin signaling marks the continued uncovering of the AD pathology.
What came first, the chicken or the egg?
With all this good news, we could almost leap for joy for Meredith! If she avoids Type II Diabetes she will be in the clear!
However, although scientists are close to unveiling the root of the cause, insulin resistance has not been proven to be the sole culprit of AD development—alas, we cannot celebrate for Meredith quite yet.
While insulin resistance does not help your chances for avoiding AD, there is also a second piece to the puzzle—this being AβOs. These oxidative stress agents are also thought to cause AD.
The AβO molecule induces stress on neurons of the brain, resulting in less insulin signaling, which perpetuates stress, which leads to kinase stress response, which increases more AβO formation, which begins the cycle again.
The question becomes: Which came first, the AβOs or the insulin resistance?

(#artstracts)

It could be that either/or could lead to AD, and that because one influences the other, a bad combination of the two could lead to the same result.
For example, say Meredith Grey avoids the junk food and does not develop insulin resistance via type II diabetes. She is still predisposed genetically, and she has a stressful job. The stressful job of being a surgeon could lead to an increase in AβO production, which could lead to insulin resistance in the brain, which would cause stress, and start up the AD development cycle.
Or, for example, say Meredith does hit the junk food hard. She develops type II diabetes, becoming insulin resistant. This insulin resistance is experienced in her brain as well as the rest of her body, and this begins putting stress on her neurons. The neurons respond with stress kinases, which lead to AβO production, which begins the cycle of AD development.
Either way, AD becomes the issue, and this is where the research lies.
If this is truly good news for Meredith or not is surely debatable. However, the research is showing more promising answers to our questions of the root of AD development.
The hope is that if we can get to the root, we can find a treatment for this detrimental disease.
If we can find a treatment, then surely that will be good news for Meredith. But until then, we’ll just hope she relaxes, exercises, and avoids the junk food.

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Alzheimer's disease and insulin resistance

Posted on March 1, 2016 by / 0 Comment

Research into the molecular nature of Alzheimer’s Disease has been a major focus the past 20 years, with (AD) claiming about 90,000 Americans annually. With genetic factors attributing to AD very minimal, the mechanisms of sporadic, late-onset AD is still not fully clarified. Intense research efforts have sought to identify this complex neurological disorder the past few years.

Recent research has unveiled the connection between Alzheimer’s disease and Insulin signaling, indicating a brain-specific form of diabetes. Several clinical studies have now established factors including hyperglycemia and hyperinsulinemia has correlated positively with the development of Alzheimer’s development in humans. Overall, Alzheimer’s brains have exhibited malfunctioning insulin pathways, and a largely decreased responsiveness to insulin.

After years of belief that insulin has no belonging in the brain, numerous studies have revealed insulin actions are key for neuronal survival and brain function. It is now established insulin regulates brain metabolism and energy balance in the hypothalamus, and is important for memory formation, association, and retrieval in the forebrain and hippocampus. Other functions include having neuroprotective properties and having a large role in cognitive functioning.

For the last 15 years, Alzheimer’s disease has been distinguished by a few specific characteristics: senile plaques and neurological tangles. Senile plagues are composed of large clumps of amyloid fibrils, specifically amyloid-β (Aβ) peptides. However despite a proven toxicity of these large aggregates, many post-mortem observations showed that the large amyloid plagues did not correlate well with AD symptoms. Instead, a loss in plasticity or neuronal signaling was discovered to be associated with oligomers of Aβ peptides called AβO’s. These toxins are now considered responsible for synapse loss and triggering Alzheimer’s Disease symptoms.
In conditions such as type 2 diabetes, sustained metabolic stress and inflammatory signaling lead to decreased insulin signaling and a decreased biological response to insulin. This is called insulin resistance, and this significantly impairs your body to properly store energy in your blood, so characteristically glucose levels soar through the roof with diabetes patients. Interestingly, this same process occurs in the brain with insulin signaling in the occurrence of Alzheimer’s disease. Several recent studies have linked neuropathic mechanisms triggered by AβOs to mechanisms involved in insulin resistance in diabetes.
Overall, if AD mechanisms are from the same causation as type 2 diabetes, these conditions can be prevented from occurring through maintaining a healthy lifestyle. The most important factor in preventing diabetes, and eventually Alzheimer’s disease, is limiting your amount of body fat. Developing excess weight near your abdomen has been closely linked to insulin resistance. This is because this deep fat isn’t near your skin, and is more likely to cause insulin resistance compared to fat developed on your hips and thighs.
Eating a diet of high-fiber, slow-release carbohydrates is an important step in a healthy diet. Carbohydrates have a big impact on your blood sugar levels, so having a smart approach to what types of carbohydrates you eat is important. Complex carbohydrates include foods like brown ride, whole-wheat pasta, whole-wheat foods, high-fiber cereals, peas and leafy greens.
Overall, several studies have shown a link of insulin resistance to the increasingly common Alzheimer’s disease. Insulin resistance has shown to have little genetic connections, so a healthy lifestyle and diet are key controllable aspects that will ultimately decrease your chances of Alzheimer’s disease.