Amyloid Synthesis

Alzheimer disease (AD) is the most common cause of dementia in the elderly, accounting for 65–70% of all cases (Jellinger, Janetzky, Attems, & Kienzl, 2008). The other dementias are of the Parkinson 's group, the fronto-temporal group and the vascular group. The total worldwide yearly costs for the treatment and care of patients suffering from dementia are estimated to be around 250 billion US dollars. The lifetime risk for AD between the ages of 65 and 100 is 33% for men and 45% for women with an annual increase of 1–2% in the seventh decade to almost 60% in the 10th decade with doubling every 5 years (Jellinger et al., 2008). AD is incurable, and thus represents a major public health problem. AD represents a challenge to humanity due to its relatively recent discovery, progressive nature of the illness, and complex diagnosis.

Alzheimer 's disease (AD) is a progressive degenerative disease of the brain from which there is no recovery. There are three brain abnormalities that are the hallmarks of the Alzheimer’s disease is initially caused by plaques buildup in the brain’s neurons as illustrated in figure 1. The support structure that allows the flow of the nutrients through the neurons gets damaged and ultimately there is loss of connection among the neurons and they die off (National Institute of Health, 2015). This causes the brain tissue to shrinks, which is called atrophies. All this ultimately lead the victim of this disease to face difficulties in governing emotions, recognize errors and patterns, coordinate movement, and remember. Ultimately, a person with AD loses all memory and mental functioning.

Alzheimer’s: Scientists know that during Alzheimer’s two abnormal proteins build in the brain. They form clumps called either ‘plaques’ or ‘tangles’. These plaques and tangles interfere with how brain cells work and communicate with each other. The plaques are usually first seen in the area of the brain that makes new memories. A lot of research is focused on finding ways to stop these proteins in their tracks and protect brain cells from harm.

In the early stages of this disease Reagan stated; "I have begun the journey that will lead me into the sunset of my life." Research has been underway for years and years. One of the more promising avenues entertains the idea that these amyloid plaque proteins are the cause of changes in the brain. "The damage occurs when neurons congregate and form protein masses called amyloids that are water-soluble in normal brains but undergo structural changes and can't be dissolved in Alzheimer's patients. The masses disrupt nerve cell functions and begin to cause symptoms such as the loss of short-term memory. The deterioration of the brain is accompanied by a drop-off in the production of the neurotransmitter acetylcholine, which plays a key role in cognitive functioning" (p.444). I do believe that these amyloid plaques do play a role in the changes observed. These tangles and plaques are kind of the tell-tale sign that Alzheimer's is present. The missing piece to the puzzle is, What gets the ball rolling? What causes these changes to occur? I am confident that if we can find the answers to these questions, that we can find a cure.

Alzheimer 's disease is a highly progressive and irreversible brain disorder that impairs cognitive function and eventually annihilates brain cells. “It is characterized by the development of amyloid plaques and neurofibrillary tangles, the loss of connections between nerve cells, or neurons, in the brain, and the death of these nerve cells” (nia). There is currently no cure for this retrogressive cognitive disease. Alzheimer’s disease affects approximately “4.5 million people in the Unites States and 8 million people worldwide” (pathopta). Studies show that one in eight people over the age of 65 will suffer from Alzheimer’s. Physicians and researchers alike believe that there are numerous individuals with the symptoms of Alzheimer’s whom go undiagnosed and untreated. This neurological disorder is not a natural age-related response, and those whom present with any signs and symptoms should be seen by their physician promptly. Even though Alzheimer’s affects a massive number of the

It is a disease that we haven’t cured yet but instead have only come up and still coming up with treatment strategies to alleviate its symptoms. AD was first described in 1906 by a German psychiatrist by the name of Alois Alzheimer whilst he was performing a histophathologic study of his patient’s brain, a patient who had been suffering from dementia. His patient’s brain’s autopsy brought to light the presence of two types of lesions, which are senile plaques and neurofibrillary tangles. He saw a visible difference in the brain tissue for it was severely damaged by these lesions. Since then, our knowledge of AD’s cellular and molecular alterations has increased and we have come up with various hypotheses for AD that may soon help in developing effective preventative and therapeutic strategies. One of the most prevailing hypotheses that have already leaded to a number of therapeutic approaches is the amyloid cascade hypothesis. Hence, the following essay will explore the pathology of the amyloid cascade hypothesis and the evidence for and against it. It will also touch upon current progress in clinical trials that test the

These plaques are made out of nerve cells surrounded by dying neurons. The same beta amyloid is a splice from a larger protein called amyloid precursor protein (Qué es la enfermedad de Alzheimer?, n.d., para. 5).

Alzheimer’s disease is characterized by the degeneration of the nervous system, mainly the neurons in the brain leads to nerve cell death and the loss of tissue throughout the whole brain (MacGill, 2009). Over a period, the brain shrinks dramatically, affecting almost all of its normal functions throughout ones life (MacGill, 2009). The brain size shrinks with AD and the tissue tends to have fewer nerve cells and connections (MacGill, 2009. Abnormal protein groups and structures of plaques and tangles characterize the disease (MacGill, 2009). Plagues and tangles are not able to be viewed or tested in the living brain but are able to be observed in an autopsy of an infected deceased (MacGill, 2009).

One hallmark of AD is amyloid beta plaques, large aggregates found in the patient brains composed of the peptide, amyloid beta. These amyloid

Alzheimer’s disease (AD) is a neurodegenerative disorder involving senile plaques distributed throughout the cerebral cortex and intracellular neurofibrillary tangles. These plaques are predominantly composed of beta-amyloid (Aβ), which is a 39 to 42 amino acid peptide and is cleaved from the (APP). With 1 in every 14 people over the age of

Nevertheless, both types of AD are recognised pathologically by the build-up of intracellular neurofibrillary tangles, extracellular amyloid plaques, and massive neuronal and synaptic loss (Carmo & Cuello, 2013). Neurofibrillary tangles are aggregates of hyper-phosphorylated tau protein and plaques are mostly insoluble deposits of β-amyloid, resulting from the cutting of the amyloid precursor protein (APP) (Farooqui & Farooqui, 2011). The discovery of mutations in the APP gene which cause familial AD lead to the articulation of the amyloid cascade hypothesis (ACH) (Hardy & Asllop, 1991). A large amount of evidence supports this view; however a number of findings are contrary to its proposal. As a result, Armstrong (2011) proposed a revision of the hypothesis, postulating that the main trigger for the development of the disease is the ageing of the brain and related wear and tear such as head trauma and stress; collectively referred to as the “allostatic load” (Carroll, 2002). Furthermore, a greater emphasis has now been placed on the role of small, soluble amyloid oligomers which seem to be the cause of early cell dysfunction in AD, rather than the large, insoluble amyloid fibrils. (Ferreira, Vieira & De Felice, 2007).

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.

Presenilins have 9 transmembrane domains are evolutionarily conserved integral membrane proteins. Presenilin, along with Aph-1, Pen-2 and nicastrin constitute integral components of a multi-protein protease complex, termed γ-secretase, which is responsible for the intramembranous cleavage of both the amyloid precursor protein (APP) and Notch. Many γ-secretase substrates have diverse cellular functions, including cell adhesion, ion conductance, and receptor kinase activity, to name a few. Presenilins are also known to exert γ-secretase-independent activities including regulation of the Wnt/β-catenin signalling pathway, calcium release from the ER, and lysosomal proteolysis. PS1 operates as a negative regulator of the Wnt/β-catenin signaling

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 is most likely formed by other symptoms called dementia. Dementia is not an actual disease, but has a vast range of symptoms which are precursors to many types of diseases. When dementia is detected in an individual their memory tends to decline and it becomes a hassle to complete everyday duties. When diagnosing individuals there are a series of steps taken in order to see if the individual progressed to dementia and also which disease caused those symptoms to take effect. These stages are preclinical, mild cognitive impairment (MCI) and dementia. Within the preclinical stage there are three sub-stages that deal with protein, plaque buildup in the brain called beta-amyloid. The symptoms for this stage are undetectable. Stage