With as much research as there is about Alzheimer’s Disease, there are surprisingly few conclusions as to its possible causes. Through the article of the week and classroom investigations into the different areas involving Alzheimer’s, much was learned about the possible mechanisms of Alzheimer’s but few conclusive answers were found. For example, Aβ protein segments that accumulates to form amyloid plaques have long believed to be an underlying cause of Alzheimer’s, as has tau aggregation and the forming of neurofibrilary tangles. Given the ambiguity of the causes of Alzheimer’s I was interested in finding out what treatment plans are being investigated. The alzheimer’s association has a section on their website that describes both completed and on-going studies that test different drugs in the hope of finding a treatment for Alzheimer’s: http://www.alz.org/research/science/alzheimers_treatment_horizon.asp?type=more_information . The wide array of mechanisms that these drugs work through are yet another example of how scattered Alzheimer’s research is. ACC-001 and AN-1792 are ‘vaccine’ type drugs that target the Aβ, and bapineuzamab is another drug that targets Aβ, but while still in process, researchers are still not sure if reducing Aβ levels will be an effective treatment for Alzheimer’s. Yet other drugs, such as methylene blue work to prevent tau protein aggregation. The Alzheimer’s Association also reports that a future successful treatment will include a ‘cocktail’ of different medications, each aimed at the different mechanisms of Alzheimer’s. It is interesting to note that there are still clinical trials underway that are testing drugs that act on Aβ when current research is leaning toward the conclusion that Aβ may not be one of the deep-seated causes of Alzheimer’s. Is a cocktail of medications that may not be treating a disease the best approach to treatment? Alzheimer’s research has come a long way, but there are still significant strides to be made. With improving technology and more research being conducted, hopefully the underlying cause of Alzheimer’s can be discovered and an effective treatment can also be found.
Insulin resistance?… Related to Alzheimer ’s disease? Who knew?
Usually when you think insulin dysfunction you think diabetes…not Alzheimer’s diseaseor dementia. Interestingly enough researchers have found a link between the two. As it turns out insulin may be linked to Alzheimer’s disease(AD) in more than one way. Below I will discuss the ways in which insulin resistance could be a risk factor leading to AD and
how diabetes ties in to the mix.
Image from: http://www.123rf.com/photo_9097816_old-hands-with-a-flower-on-the-black.html
What is insulin resistance?
First of all what is this so called condition of insulin resistance? It just means that the body produces insulin but for whatever reason the body cannot use it. Therefore the insulin is not doing all of its jobs that it’s supposed to do-most notably to help the body use glucose for energy. This leaves bloodstreams with elevated levels of insulin (hyperinsulinemia) and glucose(hyperglycemia). Insulin resistance can be caused by many interacting factors including excess weight, lack of exercise, and most importantly genetic make-up. For more information about insulin resistance please visit: http://diabetes.niddk.nih.gov/DM/pubs/insulinresistance/
How does this lead to Alzheimer’s disease?
Well the truth is we don’t exactly know yet. But from research that has been conducted so far we know that insulin resistance may be a strong indicator for people who are at the highest risk for becoming AD patients. Insulin is very important when it comes to cognitive function and aging. When insulin is being released but cannot be used by the body or brain, cell damage takes place. High abnormal levels of insulin can lead to increased risk of memory loss and brain cell degeneration such as AD. Over a long period of time the overabundant amount of insulin present in the brain becomes neurotoxic. This means that brain cells are being poisoned by these high levels of insulin. This can lead to the a poor functioning blood brain barrier (which plays a major role in brain protection) as well as insulin receptor dysfunction which ultimately puts people at high risk for AD.
Another important connection to make between insulin and AD is insulin’s relationship with the build-up of amyloid beta (Aβ) plaques. For you who are not familiar with Aβ plaques, they are formed by proteins that flock together and attach to brain cells and cause cell death. As of now Aβ plaques have been found in all AD patients. These plaques increase formation in the presence of high levels of insulin, which is initially caused by insulin resistance. The protein that breaks down these plaques is disrupted by high levels insulin and cannot do its job properly. So we get in large amount of plaques in the brain eventually resulting in AD or some type of dementia.
How can we prevent AD?
There are so many factors that lead to AD especially because insulin plays such a diverse role in the body’s metabolism. Genetics also plays a strong role in susceptibility and risk of AD. The best way reduce your risk, regardless of your genetic make up, is to stay active physically, mentally and socially while eating a healthy balanced diet. More healthy tips to reduce the risks of insulin resistance and can be found at: http://www.helpguide.org/elder/alzheimers_prevention_slowing_down_treatment.htm
How Old do We Want to Be?
This week’s topic concerns topics concerning insulin and Alzheimer’s disease deals largely with aging. Alzheimer’s is not alone with a strong correlation between age and occurrence. The chances of developing cancer and other major neurodegenerative diseases also greatly increase with age. There is little doubt that curing these diseases would led to an average extended lifespan in humanity along with improved quality of life, after all no one wants to feel the pain from cancer or forget what their children look like. These diseases dealing with life expansion seem to be “hot topics” in medicine as of late and have received much media attention. They bring a few questions to mind that I think are worth acknowledging. How far should medicine and research go with life extension? I believe that life extension is to a certain extent a by-product of well-practiced medicine and successful research but is there a limit to how “how far we go”? Or do we go with the school of thought that pursues life extension and higher quality of life.
The second question is perhaps more immediately relevant. There is only a fixed amount of money allocated from our government and other sources towards scientific research. Two categories which disease could be broken down into are those ages related mentioned earlier and the diseases acquired earlier in life for example down-syndrome. I think that cancer and these neurodegenerative diseases receive the attention they do because of their prevalence; they are much more common than obvious genetically debilitating diseases. Should our government be giving as much attention or funding as they do towards these diseases? Or should we be concentrating more on disease which affect our younger population?
Just another bullet point to the list of why we need to eat better and exercise!
- 25 million Americans have type II diabetes
- 16 million Americans will have Alzheimer’s disease by 2050
Did you know that two of America’s biggest health problems: Type II Diabetes and Alzheimer’s Disease, may be linked? On Sept. 19, 2011, NBC nightly news ran a news story about insulin being the “common culprit” between the two diseases. Check out the link below to watch the news story.
MSNBC video: study reinforces Alzheimer\’s/diabetes link
In Neurochemistry class this week, students looked more deeply into this possible link and raised some interesting questions. Why do we age? It turns out that signaling from insulin plays a role in causing “normal lifespan” – meaning we age. If there is a link between aging and age-related diseases such as Alzheimer’s disease, should we look at trying to slow down aging? What would this look like and what effect would that have on society? In addition, like the above story mentions, insulin signaling is involved with the formation of the amyloid-beta plaques that are the hallmark of Alzheimer’s disease. How exactly does insulin act and could we manipulate its actions to treat Alzheimer’s disease? Time will tell, but given the difficulty in this country to eat well and exercise, we may need to simply find a way!
Neuroscience is King
To study the brain apart from the mind, or to study the mind apart from the brain is a paramount mistake, both academically and personally. Yet there are people who do this. The guilty studiers of the brain wonder incredulously at the mind, treating it like it’s beyond the purview science. The guilty studiers of the mind are perhaps the guiltier party. They are usually altogether ignorant of the brain, or treat it offhandedly, as some organ that’s workings only correlate with those of the mind; the thing of real importance.
I held a brain in my Behavioral Neuroscience class the other day. I knew I was studying me. It knew it was studying it. I imagined at that moment the neural pattern in my brain that corresponded to my knowledge of my brain. I made note of the irony. There was at first an aversive reflex away from that knowledge. But this hardly stopped me from learning. I wasn’t going to let some intuition of mine keep me from knowing me. But I’m convinced that the brain has a secret it doesn’t want itself knowing, and it doesn’t seem like the studiers of the brain have fully grasped exactly what this secret is.
Neuroscience has a burden that no other field of science has right now. It has to deal directly with this secret. This secret will force us to redefine ourselves. Our identity, our soul, whatever we value about our precious egos, neuroscience can manipulate, change, break apart, better, worsen, and destroy. “Identity recreation,” “perspective alteration,” “mind transplant,” “thought control” will all be a new words used in the way, “mood alteration” is used now. People either see this as implausible, or too far in the future to attend to. But neither is true, this technology will arrive in our lifetimes. And humanity doesn’t have the time to brace itself for this blow. Can we properly engage in neuroscience class without understanding the risk we take in studying this material? Can we sit naively back studying something we should all be afraid of? Can we reconcile ourselves? Can we give up our egos?
Despite these concerns, no one is going to give up knowledge. Perhaps we do know what we’re up against and are just choosing to ignore it. I for one won’t preserve the secret. I’ll do just what every other good neuroscientist will do: learn the brain. There is no split any more. Mind/Brain. There is just our control over it. Neuroscience could just as easily be defined as the science of controlling ourselves. In 30 years, 50 years, anyone’s free to estimate, it will be the neuroscientist who has more power than anyone. The dexterous neuroscientist will have a better argument than anyone’s ever had. Feel free to think of an argument for something. Make it an argument that convinces everyone. Make it an argument so logically sound, so intuitively obvious, that someone would have to be crazy to deny it. The neuroscientist will have the power to make you doubt it; to make you change your mind. It’s not about right or wrong; it’s about power.
Marijuana, THC, and Medicine
The endocannibinoids play a vital role in regulation most of your brain and body functions. Without endocannibinoids, we are unable to function properly. Endocannibinoids are a family of molecules synthesized in your body that are found in the nervous system. The most common are anandamide and 2-arachidonoyl glycerol (2-AG). But they are not the only chemicals that can activate signaling in the brain, so can Marijuana.
Tetrahydrocannabinol, or THC, is commonly known for being the active ingredient found in marijuana. (Click to see the structure for those who are organically inclined)
Despite it the bad reputation it gets (not pointing any fingers), THC is useful for more than just getting high. A recent study in the Journal of Clinical Investigation by Salazar et al. shows that “Δ9-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy.” Glioma is a type of cancer specific to the brain and spinal cord. It’s named after the cells that cause it, glial cells. Glial cells are found primarily in the brain, and it is their irrational growth that causes the tumors to form. Basically, the THC gets into the signaling pathway of the cancer cells and tells them to destroy themselves. It is very cool stuff and great for the future of treating deadly cancers.
Another study from Scripps Research Institute, shows that THC is helpful in the treatment of Alzheimer’s Disease. THC stops the formation of protein buildup (amyloid plaque), by inhibiting acetylcholinesterase (AChE). AChE fosters the development of the protein buildup which causes inflammation of neurons in the brain. This is believed to be how Alzheimer’s disease is caused. This research is very interesting, and can lead to studies of novel new treatments.
If you want further information on the recent developments on THC and the endocannibinoid system, the Society for Neuroscience put out a great article on cannabis, and its applications for future research and the treatment of disease, obesity, cancer, pain, and anxiety. (http://www.sfn.org/skins/main/pdf/brainbriefings/BrainBriefings_Dec2007.pdf)
MS's new treatment?
Multiple sclerosis (MS) is an autoimmune disease that attacks the central nervous system and is often a disabling disease. The body begins to attack the fatty layer that surrounds and protects the nerve fibers in the central nervous system known as myelin and it can also damage the nerve fibers themselves. Symptoms range from numbing of limbs, fatigue, motor and coordination problems, vision problems, pain, and unusual muscle tension known as spasticity just to name a few.
There are many different types of treatment for MS including interferon, a type of chemotherapy, massage therapy, acupuncture, and chiropractic therapy. But there is a new type of treatment that is still in the “development” stage, it’s marijuana. Cannabis sativa (marijuana) is still in the study stage but it is thought to manage symptoms like pain, tremors, and spasticity. Early studies used tetrahydrocannabinol, THC, in its oral form because they could control the dose. What they wanted to see was how THC managed spasticity, tremor, and balance. The results of these studies however did not give any definitive answer. Each patient reported different results and different side effects for each symptom that was being studied.
For spasticity, mixed results were found because some patients reported feeling less spasticity, unfortunately these results could not always be confirmed by testing done by physicians. Also the effects of the THC lasted at the most three hours and came with multiple side effects including weakness, dizziness, mental clouding, coordination problems, short-term memory impairment. For tremor, a small study was done with eight severely disabled patients. Five of the eight patients reported improvement in their tremor and all eight reported experiencing a “high”. Unfortunately, in the balance category, a study found that THC actually worsened the person’s control of their posture and balance in both people with MS and people without MS.
These studies show both the good and the bad sides of marijuana use in the treatment of multiple sclerosis. But what it shows most is that much more research needs to be done. Cannabis could be a strong treatment for people suffering from MS symptoms or it could be another “treatment” that offers more side effects than results. Only time will tell.
1) http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-ms/treatments/complementary–alternative-medicine/marijuana/index.aspx
Anorexia and Cannibinoids
You know what really grinds my gears? Anorexia nervosa. Anorexia nervosa is a widely known eating disorder that afflicts around 8 million Americans a year. Anorexia results from a low appetite or a strong fear to lose weight. A possible way to cure this problem is to stimulate the appetite of those afflicted.
Enter cannabinoids. Endocannabinoids are natural occurring chemicals that occur within our body that play key roles in the body, including blocking pain, modulating motor function, and other neuroprotective roles. You may recognize the root “cannabi” from the plant genus cannabis, also known as marijuana, pot, or ganja, which is an external source of cannabinoids for the body. The active ingredient of marijuana is tetrahydrocannibinol (THC). The THC content of marijuana determines how potent a certain species/hybrid of marijuana is. THC binds to cannabinoids receptors, which can result in the properties listed above.
Another way cannabinoids affect the body is through the stimulation of appetite. I am sure you are aware of the “munchies”, the tendency of marijuana smokers to get hungry when they are high. This is at least partially due to the received cannabinoids activating the natural endocannabinoids receptors in the brain, which stimulates appetite and stabilizes body weight. Endocannabinoids also stimulate the liver into increased fat synthesis. By stimulating appetite and converting food into fat at a higher rate, cannabinoids can allow users to gain more weight.
Now, I’m not necessarily saying that the best cure for anorexia is lighting up. THC can be created synthetically and taken alone. There can be drawbacks to taking too much cannabinoids. Higher levels of cannabinoids can induce euphoria, tolerance, or neurotoxicity. However, if taken moderately, cannabinoids can effectively treat anorexia.
1) http://www.macalester.edu/psychology/whathap/UBNRP/cannabinoid06/index.html
Canninbinoids: Saving the Brain
The endocannibinoid system has very complicated interactions within the brain. A very important role of this system is to control the rate of synaptic transmissions. They are the resistors of the brain, just like in an electrical circuit. Neurotransmissions can’t go at max speed all the time, the neurons will burn out, plus it is not necessary to constantly be transmitting at max speed. The endocannibinoid system saves on the resources that can be limited in the body and saves the neurons from the wear and tear of synapses. Marijuana tunes these resistors, by adding different concentrations of different cannibinoids into the cleft. Since all cannibinoids have similar properties to a certain extent, they will all react with the CB1 receptors in some way, and can activate G-proteins, which can lead to different activations or inhibitions of pathways.
I think that if we could study the processes and connections of this system and understand it better, we could be able to enhance the productivity of this system. This could lead to advancements in the treatment of different diseases and help in the full recovery of head injuries like concussions.
Athletes and Marijuana?
From high school to professional sports, it seems like we are hearing more and more about concussions these days. But what actually is a concussion? According to WebMD, a concussion is “any type of brain injury that is caused by a blow to the head or body, a fall, or another injury that jars or shakes the brain inside the skull.”1 Indeed, the reason we are hearing more about concussions from our favorite sports teams is because they are becoming more and more common. According to Saint Clare’s Concussion Center for Children and Adolescents, “From 1997 to 2007, ER visits for concussions doubled for ages 8-13 and tripled for ages 4-19”2. Furthermore, “Each year, an estimated 3.8 million concussions related to sports/recreation occur in the United States.” That’s a lot of brain injury! And with so many injuries, athletes are itching to get back into the game. Are there any potential treatments to decrease healing time?
Marijuana?
Yeah. Marijuana. According to a recent paper published in Current Pharmaceutical Design3, endocannabinoids, or molecules in our body similar to an ingredient in marijuana, may have neuroprotective effects. THC, marijuana’s pseudo-endocannabinoid, can bind to receptors in our nervous systems, stimulating many different outcomes.
Endocannabinoids have been shown to decrease over-stimulation of brain neurons. This is important because they can enhance neuron survival in a situation of traumatic brain injury. Furthermore, the endocannabinoid system seems to have an effect on neurogenesis, or the creation of new neurons. This could potentially shorten concussion-related healing time. Additionally, the endocannabinoid system seems to be neuroprotective through signal transduction systems. This means certain molecules are turned on and off inside the cell to promote neuron survival. Lastly, endocannabinoids may be neuroprotective through their effect on another brain cell, microglia. Microglia induce inflammation which, in some cases, can further damage neurons. By blocking microglial activation, endocannabinoids, or marijuana’s active ingredient THC, could protect the injured neurons.
Of course, this is just one side of the story. Understanding of medical marijuana and its involvement in the nervous system is still unclear. While it shows promise in some instances of nervous system impairment, it shows potential deleterious effects in others. However, these findings suggest that we may someday think of marijuana in a new light.
1. http://www.webmd.com/brain/tc/traumatic-brain-injury-concussion-overview.
2. www.saintclares.org/concussions
3. Galve-Roperh, I., Aguado, T., Palazuelos, J., Guzman, M. Mechanisms of control of neuron survival by the endocannabinoid system. Current Pharmaceutical Design 2008; 14: 1-10.