Breaking down the cause underlying the pain associated with Alzheimer's disease
Compared to the brain of a healthy adult (left) the brain of someone with Alzheimer’s disease (right) has a significant reduction in volume in the cerebral cortex and hippocampus. The cerebral cortex is the most developed part of the human brain, is where information is processed, and is involved in thinking, perceiving, and producing language. The hippocampus is involved in regulating emotions and associated with creating memories.
Alzheimer’s disease is, in my opinion, the most emotionally devastating disease for both the individual with the disease and for the surrounding family and friends. Watching the person you love slowly lose grip with reality and forget who you are, your memories with them, and the connection between the two of you is utterly heartbreaking. About 5% of the population greater than 65 years old and up to 50% of the population over 85 years of age have Alzheimer’s disease. Unfortunately, death often occurs about 10 years after symptoms begin to present themselves. This is often due to loss of mobility and self-care that is associated with dementia. This post will focus on explaining what Alzheimer’s disease is, how it can be prevented, and the current treatment options available.
What is Alzheimer’s Disease?
Alzheimer’s disease is one type of neurodegenerative disease that is characterized by a loss of short-term working memory. Working memory plays a critical role in how we process, use, and remember information on a daily basis. Alzheimer’s therefore impacts our ability to recall events, especially recent ones, and leads to a loss in the ability to learn. In contrast, long-term procedural memory is not as impaired. As its name implies, procedural memory is responsible for knowing how to do things and perform routine procedures like riding a bike, walking, and talking.
Histology section demonstrating buildup of Aβ in the brain and blood vessels of an Alzheimer’s disease patient.
On the molecular level, Alzheimer’s disease is distinguished by an accumulation of a protein called amyloid beta (Aβ). The function of Aβ remains unclear in healthy individuals, but it seems to play a role in protecting against oxidative stress and regulating the transport of cholesterol. In the Alzheimer’s brain, abnormal levels of Aβ clump together to form plaques between neurons and disrupt neural communication. Modern day research is focused on understanding how these Aβ plaques influence the development of Alzheimer’s and at what stage of the disease they present themselves.
Alzheimer’s disease is also marked by buildup of a protein called tau inside neurons. Healthy neurons are generally internally supported by structures called microtubules that help guide molecules from the center of the neuron body to its opposite end where it can communicate with other neurons. In healthy neurons, tau binds to and stabilizes these microtubules. However, in Alzheimer’s disease tau detaches from microtubules and accumulates with other tau molecules. This takes on the form of a thread-like appearance that creates tangles inside the neurons. These neurofibrillary tangles ultimately block the neuron’s transport system which accelerates the progression of the disease by interrupting the communication between neurons. Moreover, abnormal tau accumulates in specific brain regions involved in memory, such as the hippocampus and temporal cortex. The number of neurofibrillary tangles and Aβ plaque accumulation has been correlated with memory loss.
An example of a neurofibrillary tangle (inside black box) that disrupts communication between neurons, leading to their death.
What Causes Alzheimer’s Disease?
Around 95% of Alzheimer’s disease cases are idiopathic, which simply means that we do not know what causes it. The remaining 5% of Alzheimer’s disease cases are termed early-onset Alzheimer’s since they occur in individuals younger than 50 years old. Early-onset Alzheimer’s disease has an identified genetic basis. Mutations in the genes presenilin 1/2 (PSEN1/2) and amyloid precursor protein (APP) have been linked to early-onset Alzheimer’s disease. Functional copies of these genes are necessary to process Aβ and prevent its accumulation. A specific mutation in the gene apolipoprotein E (APOE) has been linked to late-onset Alzheimer’s disease. APOE functions in processing fats and also enhances the breakdown of Aβ. Genetic testing could make it possible to look for mutations in these genes to determine who may be at risk for developing Alzheimer’s disease.
How Can Alzheimer’s Disease be Prevented?
A positron emission tomography (PET) scan of the brain in a healthy and diseased individual. This type of scan measures brain metabolism and activity. There is a clear and significant reduction in activity throughout the cerebral cortex in the Alzheimer’s diseased brain.
Although the risk and severity of Alzheimer’s disease worsens with age, this disease is not aging. In other words, not everyone who lives to old age will develop Alzheimer’s disease. Some of the unavoidable risk factors for Alzheimer’s disease include aging, a family history of Alzheimer’s, and having mutations in PSEN1/2 and/or APP. Modifiable risk factors include engaging in lifelong learning and cognitive training; exercising regularly; managing the risk of cardiovascular disease, diabetes, obesity, smoking, and hypertension; and habitually consuming a healthy diet. Staying mentally and socially engaged has also been shown to reduce the risk of Alzheimer’s disease. Another factor that increases this risk is having severe or repeated traumatic brain injuries (TBI). A moderate TBI appears to double the risk of having dementia, while a severe TBI increases it by 4.5 times.
What are the Current Treatment Options for Alzheimer’s Disease?
At the moment, there is no known cure for Alzheimer’s disease since the death of neurons cannot be reversed. However, there are a few drugs that are currently available to help manage the disease. The Alzheimer’s Association states that effective management of any conditions apart from the Alzheimer’s itself (e.g. diabetes and hypertension) are critical in ensuring a better quality-of-life. Additionally, regularly being involved in support groups and partaking in day-care programs will make it easier to deal with the disease.
From a pharmacology standpoint, a few drugs are clinically available to help reduce the symptoms and improve quality-of-life. A chemical called acetylcholine is reduced in the memory areas of the brain in Alzheimer’s disease patients. This acetylcholine is broken down by a protein called acetylcholinesterase. Therefore, acetylcholinesterase inhibitors are approved for symptomatic relief in order to prevent the degradation of acetylcholine. Donepezil (Aricept), rivastigmine (Exelon), and galantamine (Reminyl) are all examples of acetylcholinesterase inhibitors that provide some relief of symptoms in mild to moderate cases of Alzheimer’s disease.
