Imagine this: You have been put in charge of a crew that must dig an underground tunnel across town. The tunnel is going to be narrow, just big enough to stand in. Somehow you have to get the work crew, generators, lights, and tools in and the rocks and dirt out. If you can imagine how difficult this would be then you have some sense of how hard it is for the neurons in your brain to stay healthy. Neurons have long, thin tubes called axons that they use to send messages. To do this they need lots of energy and supplies. But, much like the tunnel project, how do the neurons transport all these materials? Understanding this problem can help us understand Alzheimer’s disease.
There are 5.5 million cases of Alzheimer’s disease in the US. Almost all of these case are in individuals older than 65 years. Two-thirds are women and Alzheimer’s disease is more common in African Americans and Hispanics compared to European descendants. Alzheimer’s disease is a progressive, degenerative neurological disorder. The hallmark symptom of the disease is memory loss but a collection of symptoms occur depending on what brain areas are affected and to what extent. Other symptoms can include personality changes, issues communicating, and an inability to recognize people, including loved ones. As the neurological degeneration progresses the individual’s symptoms worsen.
The human brain is unique. While it makes up only about two percent of our body weight it uses a full 20 percent of our daily energy. In other words, the brain needs enormous amounts of cellular energy to work properly. It also means that the brain has a lot of oxidative stress to deal with. You might think of oxidative stress like the exhaust fumes from an engine. Just like digging that underground tunnel, meeting the neuron’s energy demands presents an engineering problem. If you were in charge of the tunnel project you might set up a railway system to bring gear and workers in and the dirt out. Your neurons do something very similar. They construct a railway system made of microtubules.
With these massive energy requirements, the brain is very sensitive to any changes in the hormonal control insulin has over blood sugar. Alzheimer’s disease starts when the process of taking fuel from the bloodstream and converting it to a usable form becomes impaired. As the brain’s energy production falls behind a set of chain reactions begin. Although, there may be years between the first lag in energy production and the first symptoms. Slowly, the cellular hallmarks of Alzheimer’s disease begin to appear. Those microtubule railways become blocked by what are called neurofibrillary tangles. These tangles are made of a protein called tau protein that is supposed to help build the railways. The tangles block the delivery of nutrients down the long thin axons. The neuron doesn’t get the energy and resources it needs and it becomes stressed. The circuits between neurons that make up memories and perform important brain functions begin to break down. Eventually, the neuron will die. It is here, among the stressed, energy-starved, and dying neurons that oxidative stress increases and chronic inflammation develops. This begins a cycle where more damage to the neurons begets even more damage.
The neurons begin to secret plaques made of beta-amyloid peptides. These plaques build up around the cells and, in the Alzheimer’s brain, they are not properly broken down and cleaned-up as they are in healthy brains. As the disease progresses these plaques further block the flow of resources. As more and more neurons die the brain shrivels. The hippocampus, an area of the brain which is crucial for memory, is hit hard by Alzheimer’s disease. As the hippocampus shrivels it causes memory failure and dementia.
There is no cure for Alzheimer’s disease. The neurofibrillary tangles and the beta-amyloid plaques are often the targets for drug development but, to date, none are effective in fighting the disease. There are other treatments that can address the symptoms only, but unfortunately, these treatments do not stop the overall progression of the disease.
The connection between Alzheimer’s disease and cellular energy production is receiving more and more attention. The term type III diabetes is being used specifically to highlight the role that insulin resistance and impaired sugar metabolism play in the disease process. In the past, when Alzheimer’s disease was less common, it was seen as a stroke of unfortunate luck. Emphasizing the role impaired energy production helps medical professionals and patients reframe Alzheimer’s disease as something that is intimately tied to lifestyle factors. This opens the door to other treatments and preventative measures that involve lifestyle, nutrition, metabolism, and exercise. Afterall, long before symptoms appear the first sign of Alzheimer’s disease is a change in the way neurons use energy. This means that the time to think about prevention is, likewise, long before symptoms appear. Alzheimer’s prevention isn’t just for those who just blew out the candles on their 65th birthday cake. Rather, it becomes one more reason to target lifestyle changes at any age. Here is a list of habits for Alzheimer’s prevention from the National Institutes of Health that are appropriate for people of all ages.
● Exercise regularly.
● Eat a healthy diet that is rich in fruits and vegetables.
● Spend time with family and friends.
● Keep one’s mind active.
● Control type 2 diabetes.
● Keep blood pressure and cholesterol at healthy levels.
● Maintain a healthy body weight.
● Stop smoking.
● Get help for depression.
● Avoid drinking a lot of alcohol.
● Get plenty of sleep.
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Kodl, C. T., & Seaquist, E. R. (2008). Cognitive Dysfunction and Diabetes Mellitus. Endocrine Reviews, 29(4), 494–511. doi:10.1210/er.2007-0034
Raichle, M. E., & Gusnard, D. A. (2002). Appraising the brain’s energy budget. Proceedings of the National Academy of Sciences, 99(16), 10237–10239. doi:10.1073/pnas.172399499