Glial Activation And Proinflammatory Cytokine In Alzheimer's Thesis : Case Study

Although Alzheimer’s Disease (AD) is the most widely known cause of dementia in the elderly population, there are many other explanations and clinical diagnoses that

As a disease resulting in the loss of high cognitive functions, the Alzheimer’s disease affects brain cells and the nervous system of the body. A better understanding of the neurotransmitter, drug use to treat the disorder, and the possible side effects will bring reasoning to the possible actions of a person with the disease.

“Alzheimer’s Disease (AD) is a type of dementia, which is affecting the population that develops in the brain and can lead to problems with memory, thinking and behavior”. The Amyloid Hypothesis claims that the build up of the beta-amyloid in the brain is a cause in the development of Alzheimer disease in patients. This plaque of the beta-amyloid and its cascade of events can be linked to the deterioration and negative effects of cognitive function of the brain over time. The beta-amyloid is described to be a “sticky” protein located in the brain therefore plaques or build up of the amyloid is common. These plaques in turn can block the brain cells from communicating with each other. Which then activates an immune system, that leads to inflammation

“Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest tasks individuals with AD may start having symptoms their mid-60s” (nih.gov). AD is a multifactorial and progressive neurodegenerative disease. “Parts of AD, for example, increased oxidative state, amyloid plaque deposition, and neurofibrillary tangle of tau protein in the central cortex the limbic system of the brain, have been related with Alzheimer 's disease. The disease was once thought to be a natural part of aging; it is an extremely incapacitating type of mental dementia. Albeit, some dementia

Unfortunately the most accurate diagnosis of Alzheimer’s disease is by postmortem examination of the brain. The disease itself is not well defined, and its varied yet subtle manifestations lend difficulty in distinguishing it from other nervous system diseases or dementia-causing diseases. The danger exists that appropriate therapy that might bring relief or even cure, might be withheld from some patients if their conditions are misdiagnosed. Because, even though no effective treatment for AD is available, there are useful therapies for various diseases that produce symptoms of dementia (4).

Alzheimer’s disease is among the sixth top leading causes of death in the United States and even with an estimated 4.5 to 5.4 million suffering from Alzheimer’s disease (AD) not much is known about the causes. Only the symptoms are addressed. The main characteristics of AD are degeneration of the ability to remember, reason, communicate and with loss of motor skills and function (Piazza-Gardner, 2013). Cognitive function that is lost and is accompanied by other physiological conditions such as depression, anxiety, irritability, aggression and inappropriate behavior for a setting or location that occur in most AD suffers (Senie, 2014). AD was noted as abnormal clumps and a bundle of proteins in the brain which was discover in patients with

In general, each neuron releases a single type of neurotransmitter. Neurons that release the neurotransmitter acetylcholine are called cholinergic neurons and degeneration of cholinergic neurons in the brain are associated with Alzheimer’s (Sherwood). Drugs classified as short-term cholinesterase inhibitors are used to treat Alzheimer’s because the drugs prolong the effect of acetylcholine. There are special cells called microglia that are associated with Alzheimer’s disease as well. Microglia are immune defense cells in the CNS (central nervous system) or brain and spinal cord. The remove foreign and degenerate material in the CNS. Overactive microglia appear to be involved in a variety of inflammation-related disorders like Alzheimer’s (Sherwood). Inflammation is triggered by the body’s immune system and is a factor that plays in the progression of the disease (Alzheimer’s Disease & Dementia).

Ultimately, the path to effective new treatments is through clinical trials (“Medication”). “Future Alzheimer's treatments currently work by temporarily improving symptoms of memory loss and problems with thinking and reasoning” (Mayo Clinic Staff). “Future Alzheimer's treatments are focused on combinations of medications like those used for many cancers” (Mayo Clinic Staff). An ongoing clinical trial conducted by the Dominantly Inherited Alzheimer Network (DIAN), is testing whether antibodies can reduce the growth of beta-amyloid plaque in the brains of people with certain genetic mutations and thereby reduce, delay or prevent symptoms

Alzheimer's Disease is a condition that affects 50% of the population over the age of eighty five, which equals four million Americans each year. It is becoming an important and high-profile issue in today's society for everyone. There are rapid advancements being made in the fight against this disease now more than ever, and the purpose of this essay is to educate the public on the background as well as the new discoveries. There are many new drugs that are being tested and studied every day which slow down, and may even halt the progress of the disease.

Microglia, in the same way as vascular cells, can bind to Aβ resulting in an amplified production of cytokines, glutamate and nitric oxide (6, 7). Some studies suggest that chemokines can recruit monocytes from the peripheral blood into plaque bearing brain.(8) Related to this neuroinflammation are the alterations of type I and type II Interferon (IFN) levels in AD mice model, PDGFB-APPSwInd (J20), where an enhanced type I IFN signaling at the brain barriers and hippocampus, and decreased type II IFN response, only at the barriers were observed.(9) Of interest the blockage of IFN type I response at the central nervous system is able to partial revert the cognitive decline in aged mice.(10) However the role of this blockage on an AD mice model is still

The dilemma of approved drugs for Alzheimer's only mask the symptoms of the disease, but do not treat the primary disease or many medications delay the progression and also cause side effects in a substantial number of treated patients. A novel Alzheimer's drug would actually treat the underlying disease; either delay or inhibit cell damage which ultimately leads to the emphasis of the associated symptoms.

Alzheimer’s disease (henceforth: AD) though has four approved drugs, yet still treatment remains ineffectual and as such continues to pose a great burden to families of affected individuals, societies as well as developed countries. The complexity of the pathogenesis of AD makes it difficult to ascertain its cause along with effective treatment.

The tracks are no longer straight, and they fall apart. As a result, supplies cannot move through cells, and connections between cells are lost (alz.org). The lost connection between cells causes neurons to die. Damage first takes place in the hippocampus, which is an area in the brain responsible for memory. As more neurons die, other parts of the brain are affected. The brain tissue in the hippocampus shrinks severely, as well as the cortex, affecting thinking, planning, and remembering (alz.org). Chronic inflammation in the brain is another result from the disease. Research suggests that it may be caused by the buildup of glial cells (NIH). In a healthy brain, microglia destroy waste and toxins. In a damaged brain, microglia fail to engulf waste and protein collections, including beta-amyloid plaques (NIH). It is unknown why microglia fail to do this, but one study that researches are focusing on has to do with the TREM2 gene. In a healthy brain, TREM2 tells microglia to destroy beta-amyloid plaques and also helps control inflammation in the brain, while in a brain where this gene does not function normally, plaques build up in the brain outside of neurons

Feng Li Yang1,2, Shu Fang Ning2, Zhao Xiong Wang1, Zhu Nan Li1, Xiao Shan Li1*, Gong He Li2§

temporarily help memory and thinking problems in patients. (7, p.1046). Additionally, the effectiveness of these drugs varies between patients (3). According to the Alzheimer’s Association there are several promising new drug therapies in the development stages that may be more effective in stopping the disease progression and ultimately curing Alzheimer’s patients. Two drugs, in particular, in the research stage, show exciting potential. The first, Solanezumab, is designed to lower the levels of beta-amyloid in the brain thereby stopping the damaging plaques from adhering to brain tissue. The second, CSP-1103, is a microglial modulator that targets inflammation in the brain and also works to prevent beta-amyloid from being deposited on brain tissue (3).