Alzheimer’s Disease

Judith Tunney

Dr. Samuelsen

BIO322

April 29th 2019

Many diseases affect the brain; we also have disorders that affect the brain and the nervous system. Dementia is a common symptom of brain diseases. Dementia is the loss of mental functions such as thinking, memory, and reasoning that is severe enough to interfere with a person’s daily functioning such as paying bills. Dementia is a group of symptoms that are caused by various diseases or conditions. Alzheimer’s disease is the most common cause of progressive dementia. Alzheimer’s Disease is a condition that affects the brain by destroying the brain memory slowly, affecting thinking ability and with time the patient then gets to a state where performing simple tasks becomes a big problem. It is hard for a patient to notice that they are developing the Alzheimer disease since it starts as a simple memory loss and with time the patient then develops dementia. It progresses slowly, to a point where the affected person finds it hard to think and remember things and eventually cannot remember the basic information that a three-year-old child can remember. Mild cognitive impairment can also result in Alzheimer since it is at an intermediate stage between cognitive impairment and the dementia stage which is common among the elderly. Cognitive impairment leads to dementia, and after some years Alzheimer then arises (Winblad, et al., 2016)

Much research has been done to understand the root causes of Alzheimer disease but there is no detailed information to be learned. Scientific studies in existence have only established that the disease develops in stages as stated above. Alois Alzheimer first described the disease in 1907. According to him, presenile dementia, cognitive impairment, the existence of senile and neurofibrillary tangles has been defined as the key features and the tracking factors that can help in diagnosing a patient with Alzheimer (Armstrong, 2013). These features are now regarded as the clinical pathological features of the disease that is affecting the brain. There have been reasons speculated since 1907 about the disease and they include acceleration of aging. There is an age-related reduced brain capacity; thus when one ages very fast the brain capacity tends to reduce more quickly. This has never been shown scientifically. Thus it remains a theory. Also, some argue that degeneration of anatomical pathways reduces one’s ability to think and as days go by one loses his memory and eventually he or she is diagnosed with Alzheimer. Studies in the 1980s showed that there are losses in acetylcholine in the brain reducing one’s ability to think (Armstrong, 2013). Degeneration of one’s anatomical pathway comes as a result of reduced cholinergic system inters affecting the neural network thus resulting in memory loss cases. Another cause is linked to genetics where one may be a carrier or has the Alzheimer disease allele and passes it to the unborn child who then experiences the symptoms as he or she grows.

Despite the lack of scientific proof on the exact cause of Alzheimer disease, scientists have linked it to the core brain proteins which at one-point fail to work normally. Abnormal functioning of these core proteins then affects the operations of the brain releasing a series of toxic events (Lin et al., 2018). The neurons get damaged and end up losing connection to each other in return causing damage to the memory of the brain. This process is said to begin years before the signs of Alzheimer disease start to manifest. The region of the brain, which controls memory, is the one that gets damaged first before the loss of neurons spreads to other parts of the brain. Since the signs are hardly felt at an early stage when the memory part of the brain is completely destroyed, then the brain shrinks significantly, and one’s memory is damaged.

The two proteins linked to dementia are plaques and tangles. Plaques are a beta-amyloid leftover of larger proteins which when they cluster together they interrupt the functioning of the neurons and in return affecting cell to cell communication in the brain (James and Bennett, 2019). When cell-to-cell communication is lost it becomes hard for one to absorb and release information; thus what is referred to as memory loss. The clusters form amyloid plaques, which are more massive clusters that also contain cell debris. In the cell membrane of a neuron, there are amyloid precursor proteins, which helps the cell grow and repair its self. It gets used, broken down and recycled, as the protein is soluble. This process is caused by alpha-secretase and gamma-secretase cropping up the protein. If another protein (Beta-secretase) teams up with Gamma-secretase instead it means the leftover protein is no longer soluble. This creates Amyloid-Beta, the monomers are sticky and start to clump together outside of the cell to form Beta-amyloid clumps. These plaques get between the neurons and stop signaling. If brain cells can’t signal then normal brain function is seriously impaired (e.g. memory), also, starts an immune response due to inflammation around the neurons. Plaques can gather around blood vessels and cause the walls to weaken, increasing the risk of hemorrhage that is Amyloid angiopathy (The weakening of blood vessel walls, increasing the risk of hemorrhage). Tangles, on the other hand, are the Tau proteins, which aid in neural transport and internal support by carrying nutrients to other parts of the brain. Cells are held together by their cytoskeleton, which is made up of Microtubules. Tau makes sure that these tubules stay straight so food molecules can be transferred. It’s thought that the presence of Beta-amyloid plaque outside of the neuron causes the presence of Kinase. Kinase transports phosphate groups to the Tau protein and causes them to change their shape, in turn; Tau can no longer support the microtubules so they clump together to create neurofibrillary tangles. Neurons with tangles cannot signal and will undergo Apoptosis. This will cause some changes in brain structure. A person who happens to develop Alzheimer as a result of Tau changing their shape by collecting themselves into tangles which then forms structures known as neurofibrillary structures, which are toxic to the brain (James and Bennett, 2019). Interrupting the supply of nutrients to the brain hinders normal brain functioning, which then causes cognitive impairment, and as the condition the last one then gets Alzheimer.

The Apolipoprotein E gene (APOE) is the best-understood gene factor liked to Alzheimer. A variation in APOE e4 increases the risk factor of one getting Alzheimer. The gene is hereditary just the same way we understand how DNA is passed from parents. However, not all the people with APOE e4 get Alzheimer; it is only a few, but it is good to frequently visit a physician if one experiences the symptoms and has the same gene mutation. The Apolipoprotein E (APOE) gene is associated with Alzheimer’s disease. Three possible alleles exist for APOE—E2, E3 and E4. Each allele differs by one base, and the protein product of each gene differs by one amino acid. An individual with at least one E4 allele is more likely to develop Alzheimer’s disease (Lin et al., 2018). Similarly, an E2 allele means the person is less likely to develop the disease, (this is not an exact science). Many individuals with two E4 alleles never develop Alzheimer’s and two E2 alleles won’t rule out Alzheimer’s completely. Like most common chronic disorders, Alzheimer’s disease is polygenic and influenced by environment.

A good number of those with Down syndrome happen to be diagnosed with Alzheimer at an old age. Having three copies of the #21 chromosome explains the issue; thus one has three copies of the protein that leads to the formation of beta-amyloid (Kumar, and Singh, 2015). With gender, less is to be explained. However, there are more females with Alzheimer because they tend to live longer compared to males. Nearly everyone with mild cognitive impairment develops Alzheimer after some years. Thus this category is also at risk. Also people who have had severe past head trauma can easily get Alzheimer because of the frequent interruption of the neurotransmitter cells. Lifestyle for example; nonnutritional diet and lack of physical exercise, and long-term health conditions, like high blood pressure and diabetes, plays a role in the risk of getting Alzheimer disease. Diagnosis of Alzheimer is a big problem, but when one dies, true diagnosis can be obtained from the autopsy done to carry out examinations if the brain is damaged or a person’s mind was affected, and one had Alzheimer disease. However, testing allows for 90% accuracy that a patient has “probable Alzheimer disease”. The rest of the diagnosis is through studying the symptoms stated above, and if they keep recurring before one gets medicine, then there are very high chances one has Alzheimer disease. The diagnosis helps to curb problems such as incontinence and depression.

The treatment options that exist do not treat the disease but the symptoms of Alzheimer. The drugs offered do not stop the progression of Alzheimer, but to some point, they just slow down the progress. Among the medications given include; cholinesterase inhibitors where there are four types given that are, Tacrine (Cognex), Donepezil (Aricept), Rivastigmine (Exelon) and Galantamine (Razadyne). Antidepressants are also given anxiolytics and antipsychotic drugs. Cholinesterase Inhibitors slow the progression of the disease by preventing the breakdown of acetylcholine, while antidepressants—paroxetine, fluoxetine, citalopram, and sertraline-to treat irritability and mood disorders in Alzheimer patients. Anxiolytics – Lorazepam (Ativan) is used to treat any anxiety or difficulty sleeping. Antipsychotic medications aripiprazole (Abilify) and olanzapine (Zyprexa)-help in treating any hallucinations, delusions, agitation, and aggression. Nondrug therapies include vitamin E, hormone therapy for estrogen in women. Music and art therapy are also good since it relaxes the brain and neurotransmitters. Memantine (Namenda) is used to relieve advanced symptoms of Alzheimer blocks NMDA Glu receptors (Glu receptors usually let Calcium ions in), but with medication, they decrease the number of Calcium ions (Selkoe, and Hardy, 2016). High levels of Calcium ions can cause oxidative stress, apoptosis, and neurodegeneration thus by blocking this, the drug delays progress of symptoms (Kumar and Singh, 2015).

 Cholinesterase inhibitors not effective with advanced stages of Alzheimer’s because they eventually lose their effect because as the disease progresses, the brain produces less acetylcholine. Currently, there are new drugs under research in Russia where the theory behind it is there is an alteration to the amyloid protein processing in Alzheimer that involves alterations in secretase activity by using secretase inhibitors, can reduce levels of abnormal amyloid protein fragments (Alzheimer’s. 2015). Reducing the level of amyloid fragments implies that cell communication will not be lost that chances of one getting Alzheimer are law even when there is a genetic history.

Conclusively, Alzheimer is a manageable condition which when one discovers it at an early stage the symptoms can be treated, and one may get back to normal — participating in social events, engaging in physical exercises, eating a proper diet and avoiding stressful situations it the best way to prevent cognitive impairment which might result in Alzheimer. If a family in unsure, ruling out Alzheimer disease as a cause for memory deficit in a family member, diagnosis can ease concerns. Diagnosis is done to help the family have as much time to prepare and learn how to care for a family member with Alzheimer disease (Alzheimer’s, 2015). Some treatment medications are only used in the early stage, so the earlier you can diagnose, the better the treatment options. We should all show love and help those with memory problems gain back their memory through therapies and helping them seek medication.

LITERATURE CITED

Alzheimer’s, A. (2015). 2015 Alzheimer’s disease facts and figures. Alzheimer’s & dementia: the journal of the Alzheimer’s Association, 11(3), 332.

Armstrong, R. (2013). What causes Alzheimer’s disease?. Folia Neuropathologica, 51(3), 169-188.James, B. D., & Bennett, D. A. (2019). Causes and Patterns of Dementia: An Update in the Era of Redefining Alzheimer’s Disease. Annual review of public health, 40.

Kumar, A., & Singh, A. (2015). A review on Alzheimer’s disease pathophysiology and its management: an update. Pharmacological Reports, 67(2), 195-203.Lin, Y. T., Seo, J., Gao, F., Feldman, H. M., Wen, H. L., Penney, J., … & Rueda, R. (2018). APOE4 causes widespread molecular and cellular alterations associated with Alzheimer’s disease phenotypes in human iPSC-derived brain cell types. Neuron, 98(6), 1141-1154.Winblad, B., Amouyel, P., Andrieu, S., Ballard, C., Brayne, C., Brodaty, H., … & Fratiglioni, L. (2016). Defeating Alzheimer’s disease and other dementias: a priority for European science and society. The Lancet Neurology, 15(5), 455-532.Selkoe, D. J., & Hardy, J. (2016). The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO molecular medicine, 8(6), 595-608.