Alzheimer's Disease Case Study

Alzheimer 's disease (AD) was discovered by a German doctor Alois Alzheimer in 1906 when he found amyloid plaques and neurofibrillary tangles in the autopsy of a woman who died of an unknown mental disease. The extracellular amyloid plaque deposits, composed of insoluble amyloid-Beta peptide were hypothesized to be the main etiological factor. “The most important abnormality is an excess of Amyloid-beta peptides brought about through either overproduction or failure in degradation.” (Uzun, Kozumplik, & Folnegović-Smalc, 2011) Later, it was discovered that intracellular neurofibrillary tangles composed of hyper-phosphorylated, helically-paired tau

Alzheimer’s disease is named after Dr. Alois Alzheimer who first discovered deviations from normal tissues of healthy individuals in the brain tissue of a lady in 1906. The woman, who showed symptoms of erratic behavior, loss of memory, and problems with communication, died of a then unfamiliar mental disorder. This led Dr. Alzheimer to investigate the cause of her unusual death. He assessed the brain of the woman and found that there were many anomalous masses (amyloid plaques) and intertwined bundles of fiber (neurofibrillary tangles). Scientists today have pinpointed the qualities of Alzheimer’s to be a) tangles in the brain (neurofibrillary tangles), b) plaque in the brain (amyloid plaques), and c) loss of connections among nerve cells.

A common observation in the brain of people who have died from Alzheimer’s is that plaques and tangles make from protein fragments are present. (A Century of Alzheimer’s Disease)

Alzheimer’s is a type of dementia that causes complications with memory, thinking, and behavior. Long before any signs of memory loss, there a microscopic changes occurring in the brain, altering its functionality (Alzheimer 's Association Organization, 2016). The brain has billions of nerve cells that work together, and when one portion of the brains neurons are malfunctioning it leads to breakdowns in other parts of the brain. The two most noted abnormal structures that are suspected to damage and kill neurons in the brain in patients with Alzheimer’s are plaques and tangles. Plaques are deposits of a proteins fragment called beta-amyloid that build up in the spaces between nerve cells; and tangles are twisted fibers of another protein called tau that build up inside cells (Alzheimer 's Association Organization, 2016).

Alzheimer's is a neurodegenerative disorder that affects the neurons within the brain, causing memory loss as well as language, and behavioral disturbances. An Alzheimer's brain contains Amyloid plaques that form toxic proteins which are called amyloid beta. The amyloid plaques start to spread throughout the brain causing tangles to form in the brain. The tangles are a form of twisted threads of protein. In compartment to a “normal” brain with an Alzheimer's brain, that Alzheimer's brain is remarkably smaller in size and contains fluid flied spaces.

“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 a neurodegenerative disorder, it affects two pathological hallmarks: amyloid plaques and neurofibrillary tangles. “Amyloid plaques are caused when protein pieces called beta amyloid stick together, they eventually build up between the nerve cells into plaques.” (Ballard, 2011) Amyloid plaques trigger neurological dysfunction and eventually brain death. Compared to a healthy brain the amyloid is broken down and disposed, however in AD they collect and form hard plaques. “Once brain death happens there is no way for the brain to communicate, or restore memory” (Brightfocus.org, 2014). Neurofibrillary tangles are fibers found in the brain cells, and they have a primary protein called ‘tau’ which aids in the structure called microtubule. “Microtubules help move nutrients and other factors from one cell to another with Alzheimer’ the ‘tau’ protein is abnormal and the microtubule structure collapses.” (Ballard, 2014 & Brightfocus.org, 2014) Even though we often see the effects of AD on the outside; it is a neurodegenerative disease effecting the amyloid plaques and

β-amyloid aggregation spread from the site of injection to include both hemispheres of the brain further displaying the potentiation induced by aggregates within the brain homogenates (Stöhr et al, 2012). Under transmission electron microscopy, purified β-amyloid aggregates from transgenic mice revealed densely bundled fibrils; which were observed to increase levels of GFAP, Aβ(1-40) and Aβ(1-42) in bigenic mice at 300 days post injection via ELISA and immunoblotting (Stöhr et al, 2012). Crude brain homogenate exhibited approximately 15-20 times less β-amyloid than the purified homogenates (Stöhr et al, 2012). BLI of bigenic mouse brains injected with purified homogenate exhibited an early time of detection with signals at 161 + 7 [Tg(APP23)] and 173 + 9 [Tg(CRND8)] days (Stöhr et al, 2012). (FIGURE). Synthetic β-amyloid aggregates, wild-type Aβ(1-40) and mutant Aβ(AβS26C)2, were used to determine if prior results from purified brain homogenate could have contained any cofactors which would affect propagation of pathology (Stöhr et al, 2012). Results from the injection of synthetic fibrils into bigenic mice revealed similar β-amyloid aggregation, however pathology was less severe than purified brain homogenates from transgenic models (Stöhr et al, 2012). BLI of synthetic fibrils revealed a decrease in

Alzheimer 's disease is a non curable progressive condition caused by the degeneration of neurons, the main cellular component of the central nervous system. This degeneration is believed to be caused by a build up and entanglement of the functional proteins within and around the neuron. However, the exact cause of neuron

Alzheimer’s is described as a type of disease that causes mental illness, which causes problems with memory, thinking, and behavior of an individual. It is a deterioration of the nervous system especially the neurons in the brain. Alzheimers’ is the result of mutations on genes. Specifically, familial alzheimer’s is caused by a mutation in the gene coding for the amyloid precursor protein (APP) on chromosome 21q.When this gene is modified, a toxic protein fragment called amyloid beta peptide are produced in the brain. This peptide builds up in the brain and form amyloid plaques. The accumulation of this “amyloid beta peptide and amyloid plaque,” can lead to a great deal of death of nerve cells and progression of symptoms of Alzheimer’s disease (Genetics Home Reference, paragraph 6).

In 1906, Alois Alzheimer discovered Alzheimer’s disease after he studied the dead body of patient August D. An autopsy was done and found fiber tangles in the brain that is now known as amyloid plaques. During the autopsy, there was shrinkage in and around the nerve cells noted in the patient’s brain. The symptoms that August D experienced before she passed away were memory loss, paranoia, and psychological changes. Currently, the main features of Alzheimer’s disease still includes presence of plaques, tangles and the loss of connections between nerve cells in the

The Aβ plaques comprised of accumulated proteins that formed a β-sheet rich tertiary structure, promoting a self-assembling property and becoming cytotoxic. These resulting structures are very similar in from and function to amyloid fibrils. Though not the sole cause of the degeneration, this amyloid like structure is predicted to have a strong connection with the disease. Evidence has also been provided by this research group that these Aβ plaques have a highly similar de novo generation as many prion positive proteins. The Aβ aggregation begins with a seeding of misfolded proteins. In the case of Alzheimer’s disease these Aβ plaques spread through the brain’s tissue through axial propagation. This is shown when plaques are injected into a Aβ-rich brain and are seen to spread along the expected pathway of axons, from the hippocampus, to the hippocampal fissure, then the subpial zone. This research generated the conclusion that these Aβ plaques are essentially PrLPs. According to Walker the research also supports the designation that the seeds could be considered Aβ prions, as the molecular and protein properties of these match those given the yeast prions and other PrLP found throughout human disease.

An amyloid plaque is finding between the brain cells. It forms when protein pieces called Bata-amyloid- clump together. They come from large protein from fatty membrane around nerve cell. Beta-amyloid is chemically “stinky” and builds up into plaques. For a long time scientist thought that plaques might cause all of the damage to neurons that is seen in the Alzheimer disease. But now many scientists think that oligomers may be a major culprit. The other group also thinks that plaques might be a late stage of attempt by brain to get this harmful beta-amyloid away from neurons.

It has been found that the oligomeric forms of Aβ were more dangerous than its monomers, acting intracellularly and extracellularly leading to the disruption of several downstream mechanisms, such as the disruption of intracellular calcium homeostasis (Camandola

Alzheimer's Disease is a progressive degenerative disease of the brain that ultimately results in dementia, which is known as mental detoriation. Alzheimer's Disease is irreversible; it destroys memory and other important mental functions. (Smith, 2015) By knowing whom Alzheimer’s disease mostly affects makes it easier to target the disease by knowing which group it mainly targets and what we can do to help that specific group with different types of treatments. Alzheimer's Disease primarily affects individuals over the age of sixty-five. (Devine, 2015) One in every ten people over age sixty-five will develop Alzheimer's disease. (Devine, 2015) Almost half of those who reach eighty-five will develop the disease. An estimated 4.5 million American