Although the early-onset AD related to specific genetic mutations seem to have a stronger relationship to the AβH, it only accounts for less then 5% of the cases (Knopman, 2014). The other cases, classified as late-onset AD, have not be fully understood only with the advent of the AβH, although both types of AD bear plaques and tangles, hallmarks of the disease. I. What is the real role of Aβ? One of the most refutable arguments against the amyloid-beta theory is that a considerate amount of elders, particularly above 70 years of age, have amyloid plaques with no cognitive decline (Corrada et al., 2012). It is estimated that about 1/3 of old age persons without in vivo diagnosis of AD or any other dementia, have brain histopathological features …show more content…
coherent with AD (Murray et al., 2011). Extensive areas of plaques have also been identified in vivo with neuroimaging techniques without cognitive alterations (Pimpilikar, 2008). The possibility of Aβ being non-pathologic since it can be found in both healthy and deceased subjects puts the Aβ theory in question, and spurs scientists to find a different marker that is unique to patients with disease. Jicha et al. in 2005 concluded that more than 95% of persons who achieved or surpassed 100 years of age would present with AD pathology. Considering the presence of Aβ plaques and tangles is what is understood as AD pathology, if people achieve an old enough age, Aβ will be found indiscriminately within the population. Therefore the presence of Aβ would cease to be a marker of AD disease and as a consequence would fail to be the cause of it. Furthermore, the deposition of Aβ plaques is also found in patients bearing other diseases, such as Parkinson, head trauma and cerebral vascular disease (Pimpilikar, 2008). Thus leading towards the understanding that Aβ is a marker of alterations within the brain tissue, which can be induced by normal aging, AD and other brain injuries which lead directly to neuronal stress inducing metabolic modifications. In fact some researches believe that the production of Aβ is a compensation for the changes within neuronal tissue microstructures (Caughey & Lansbury, 2003). Some scientists also believe that the capability of forming tangles, associated to Aβ’s amphipathic structure, is only observed in vitro and occurs differently in vivo (Pimpilikar, 2009). Molecules with such a hydrophobic nature would most likely be transported in association with binding proteins in the human body and therefore would have a harder time aggregating and interacting with neighboring cells (Pimpilikar, 2009). The relationship between tau tangles and amyloid plaques and by which exact mechanism Aβ leads to the formation of tangles has also been discussed.
Braak & Braak established in 1998 that tangles are seen before plaques in the AD brain. Furthermore, this study observed a greater association between the amount of tangles and disease progression than when comparing the second with the quantity of plaques (Giannakopoulos et al., 2003). Besides these findings, plaques and tangles also seem to emerge from distinct areas within the brain. Tangles firstly appear in the limbic system, area that is extremely related to memory processing, and then spread to cortical regions (Pimpilikar, 2009). Differently, plaques are primarily found in the frontal cortex and then ranges the entire cortical region as disease progresses (Pimpilikar, 2009). Thus, their deposition seems to be temporally disconnected. This disruption between the presence of plaques and tangles is a caveat in the AβH, since the premises within the hypothesis are not able to explain the connection between the pathological hallmarks of the …show more content…
disease. II. Questioning the cause of early-onset AD Even Aβ’s causative effect on AD patients with overt mutations has been questioned. Some mutations in PS1 decrease Aβ40 levels and do not manage to increase Aβ42 production and still the patient has a progressive clinical and cognitive decline (Pimplikar, 2008). The release of neurotransmitters and synaptic function seem to be dependent of PS1 and 2, their loss leads to alterations in calcium channels within the presynaptic terminals, leading to a deficient neurotransmitter release (Pimpilikar et al., 2010). Furthermore, presenilins are also capable to interact with other neuronal enzymes responsible for cell proliferation, growth and signaling (Pimpilikar et al., 2010). Hence presenilins seem to have a more robust role in AD pathology, and their function is not only as cleavers of APP. III. Understanding the results of treatments against Aβ Since Aβ was thought to be the causative agent of Alzheimer’s disease, many investments were spurred into finding therapeutic vehicles to lower the expression of Aβ within the brain tissue, and as hypothesized, diminish progression of disease. The main therapeutic approaches: secretase inhibitors, Aβ vaccination and chelation therapies showed efficacy in rodent models in diminishing the amount of plaques. However in clinical trials, although these approaches lowered the quantity of neuronal plaques, that did not prevent progression of disease (Giuseppe et al., 2003). Secretase inhibitors act decreasing α-secretase activity, thus diminishing the break down of APP into amyloid (Giuseppe et al., 2003). Differently, chelators have the ability to diminish amyloid’s toxic effects, since it acts disrupting the bond between Aβ and ionic metals, which are known to branch production of ROS (Giuseppe et al., 2003; Bush, 2002). These drugs however are linked to multiple collateral effects, and specifically lead to vitamin B12 deficiency, which can lead to hematologic pathologies and to myelo-optic neuropathy (Kisilevsky, 2000; Tateishi, 2000). Lastly, Aβ vaccination is done by passively immunizing subjects.
Since the immune response plays an important role in Aβ pathogenesis, the presence of anti- Aβ antibodies could prevent the formation of amyloid plaques (Dodart et al., 2002). A few clinical trials testing Aβ vaccination were discontinued because 6% of the subjects presented aseptic meningoencephalitis, which is a severe adverse effect (Orgogozo et al., 2013). In one study however, by Hock et al. in 2003, AD patients immunized twice presented a slower progression of cognitive decline when compared to non-immunized patients, within the year of
assessment. Mixed findings in regards to anti- Aβ drug efficacy and a series of clinical trials demonstrating that even with the substantial reduction of amyloid plaques the disease did not seize to progress and that does patients with mild disease suffered no halt in cognitive symptoms after Aβ was reduced, leads to the understanding that Aβ is most likely not the cause of AD. If indeed Aβ was the primary event in the cascade that leads to cognitive decline in AD patients, there would mostly likely be a proportional dose-response reaction, meaning that depleting the causing agent would mean reducing global symptomatology and disease progression. Aβ toxic effects have been proved through animal and in vivo studies, indeed neurodegeneration suffers the effect of Aβ deposition, however it is not the only cause and the only molecule accounted for the etiology of the disease.
Although Alzheimer’s disease appears to be the most common cause of dementia, “more than 50 conditions are associated with dementia, including degenerative ...
Thesis/Preview Statement – Alzheimer’s disease (AD) causes a decline in brain function, it destroys healthy nerve cells. Today, we have discussed Causes, Symptoms, and Diagnosis of AD.
Memory plays a significant role in the everyday lives of people of all ages. It allows them to recall information and remember skills that were learned in the past. Memory also organizes past information to help people make current and future decisions. However, imagine forgetting the names of close family members or not having the ability to find your keys every time you want to leave the house. These are some of the struggles that people with Alzheimer’s disease face daily. Alzheimer’s disease was first identified by German neurologist Alois Alzheimer in 1906, and was discovered to have an overpowering effect on explicit memory loss (Gruetzner, 1988). There are two types of Alzheimer’s disease – early onset and late onset. Early onset occurs in patients who are diagnosed before the age of 65 whereas late onset occurs in patients who are diagnosed after the age of 65. In the early stages of Alzheimer’s disease, short-term memory is often lost. As Alzheimer’s disease progresses, problems with long-term memory begin to develop, in addition to short-term memory impairments. Although a lot is known about the symptoms of Alzheimer’s disease, the cause has not been conclusively identified. However, as research continues, new theories about the cause of Alzheimer’s disease are being proposed. This has led to a controversy over whether Alzheimer’s disease is caused by genetics or environmental influences (Gruetzner, 1988).
...t one has it. Many scientists hypothesize that there is an inflammatory response in the brain when there is an extensive B-42 amassing. To slow or stop this, scientists theorize that the use of anti-inflammatory drugs, such as aspirin, could delay the swelling in the brain. Also, as scientists have known that taking a multi-vitamin tablet each day is good for you, there has been recent research demonstrating that the use of antioxidants may protect neurons, not just the immune system and keeping the body healthy by providing vitamins and minerals. These special supplements protect the neurons from the effects of the accruing B-Amyloid that would likely cause the plaque that causes AD.
Alzheimer’s disease or AD is an incurable disorder of the brain that results in loss of normal brain structure and function. In an AD brain, normal brain tissue is slowly replaced by structures called plaques and neurofibrillary tangles. The plaques represent a naturally occurring sticky protein called beta amyloid and in an Alzheimer’s brain, sufferer’s tend to accumulate too much of this protein. Neurofibrillary tangles represent collapsed tau proteins which, in a normal brain along with microtubules, form a skeleton that maintains the shape of the nerve cells. In Alzheimer’s disease, the tau proteins break loose from their normal location and form tangles. Without the support of these molecules, nerve cells collapse and die. As normal brain structure is lost with progression of the disease, brain function also degenerates. Patients afflicted with Alzheimer’s disease display a gradual mental decline. Initially, and most apparently, there is a loss of short-term memory. Eventually, as a patient progresses to later stages of the disease, the brain becomes so damaged that patients can no longer communicate or recognize immediate family or even themselves. They have difficulty walking and standing and frequently fall. In the final stages, they lose bladder and bowel control and have difficulty with swallowing, frequently leaving them malnourished and dehydrated. Eventually, they are forced to remain bedridden and, without the help of life-prolonging measures provided in a hospital, die. However, this level of deterioration is severe and may take as long as twenty years. Because of the disease’s slow progress and its usual later start in a person’s life, a victim of AD will usually die first of natural causes. Under the objectives ...
There are three different abnormalities that can make up Alzheimer’s disease. The first abnormality is beta-amyloid peptide cut from APP, a membrane precursor protein (Marieb and Hoehn 2013). Too much beta-amyloid is toxic and causes plaque buildup between neurons that reduces levels of acetylcholine which makes is difficult to retrieve old memories and make new ones (Marieb and Hoehn 2013). Another abnormality of Alzheimer’s disease is the presence of neurofibrillary tangles inside the neuron. These tangles consist of tau, a protein that leaves its stabilizing role and binds to another tau molecule forming a neurofibrillary tangle. (Marieb and Hoehn 2013). Neurofibrillary tangles then kill the neuron. The final abnormality of Alzheimer’s disease is brain shrinkage. The brain shrink...
In the 17th and the 19th century dementia was synonymous with insanity. Still many knew that people with this disease suffered from permanent damage that was irreversible unlike mental disorders where the brain remains intact (2006). Dementia was often known as senile which is common with old age. Studies through the years have shown that it is much more serious and causes damage to areas of the brain. Alois Alzheimer in 1910 noticed tangles, plaques, and arterio...
Alzheimer’s disease comes from the last name of a neuro-psychiatrist from Germany, Alois Alzheimer. The disease was first diagnosed when a woman in her early fifties began experience memory problems. “Alzheimer recounted the now famous case of ‘Auguste D.’ a 51-year-old housewife who had been failing mentally for several years. As a result she had been admitted to his care in the Asylum for the Insane and Epileptic…” (Maurer and Maurer 1). After her death, he continued to examine her brain to find causes and explanations for her behavior. He discovered “…classic neuro-pathological signs of plaques and tangles” (Maurer and Maurer 1). “Plaques are chains of amino acids that are pieces of the amyloid precursor protein…tangles are aggregates of the protein tau” (Secko 1). As plaques develop they produce tangles and “these two abnormalities ultimately lead to loss of cognitive function” (Secko 1) Alois Alzheimer’s research has allowed many specialist to conclude that the apolipoproetein E gene may contribute to the disease.
This disease causes memory loss, difficulty in thinking processes, mood swings, depression, hallucinations, personality changes, and the inability to create new memories. Alzheimer’s disease is most common in people who are at the age of sixty years or older, but it can start as early as the age of nineteen. It can be categorized as a type of dementia. “Scientists believe Alzheimer’s disease prevents parts of a cell’s factory from running well” (Alzheimer’s Disease: The basics). Scientist believe that one cause of Alzheimer’s could be caused by plaques and tangles. Plaques are the build up of a protein called beta-amyloid in the nerve cells. Tangles are twisted fibers of the tau protein that build up inside of a cell. The exact cause of Alzheimer’s has not yet been determined, but scientists have reason to believe that it is because these plaques and tangles are blocking the communication of cells in the nervous system. Another probable cause is a mutation on the chromosomal genes 21, 14, and 1. This is why it is believed to be a genetically inherited
Alzheimer’s disease (AD) is one of the leading causes of death in America and there are currently more than five million people living with the disease (Alzheimer’s Association, 2014). What may be most troubling about these numbers is the fact that Alzheimer’s disease has no current cure. Alzheimer’s disease is a neurocognitive disorder and a common form of dementia that will affects a person’s memory, way of thinking and their behavior (Alzheimer’s Association, 2014). AD typically develops slowly and the more time a person has the disease the worse the symptoms will become. AD in its later stages becomes so severe that people with the disease cannot even do simple daily tasks. Although there is no cure there are still ways to prevent, delay, and possibly treat the disease.
Alzheimer's disease is the most common form of dementia, and this terminal, progressive brain disorder has no known cause or cure. Its greatest known risk factor is increasing age which is why is it is infamous for developing in the elderly, typically in ages 65 or over, however for the 5%(1) that develop Alzheimer’s in their 40s or 50s it is known as early Alzheimer’s. Because Alzheimer’s worsens over time, those with it tend to struggle with completing daily tasks especially elderly people. Given that there is no cure for Alzheimer’s, the treatments available slow the worsening of dementia symptoms and improve quality of life for those with Alzheimer’s and their caregivers. It is not known what causes Alzheimer's, however, those with Alzheimer's have been found to have abnormal amounts of protein (amyloid plaques) and fibres.(The amyloid plaques and fibres are found in regions of the brain where problem solving and thinking take place e.g The cerebrum.) Due to the unusual amounts of amyloid plaques and fibres, it reduces the effectiveness of healthy neurons and eventually, destroying them.
Scientists know that Alzheimer disease is characterized by a gradual spread of sticky plaques and clumps of tangled fibers that disrupt the organization of nerve cells in the brain. However , a definite cause, prevention, or cause has not been found.
Dementia is an organic brain syndrome which results in global cognitive impairments. Dementia can occur as a result of a variety of neurological diseases. Some of the more well known dementing diseases include Alzheimer's disease (AD), multi-infarct dementia (MID), and Huntington's disease (HD). Throughout this essay the emphasis will be placed on AD (also known as dementia of the Alzheimer's type, and primary degenerative dementia), because statistically it is the most significant dementing disease occurring in over 50% of demented patients (see epidemiology).
Alzheimer’s Disease is named after a German doctor, who specializes in the brain and nervous system, named Alois Alzheimer. This Disease forms in the brain. Alzheimer’s is the most common form of Dementia, a general term for memory loss and other intellectual abilities serious enough to enter. The Tau protein ensures the tubes in your brain stay straight allowing molecules to pass through freely. In Alzheimer’s Disease the protein collapses into strands or tangles, making the tubes disintegrate. There is visible differences of brain tissue in the from misfolded proteins called plaques and tangles. Beta-Amyloid clumps block signals and communication between cells in the brain. Researchers agree that Alzheimer’s Disease is m...
AD is generally characterized by the accumulation of amyloid-β-peptide (Aβ) plaques (which are neurotoxic) in the brain and surrounding blood vessels (Iadecola, 2004). AD has also been associated with altered cerebrovascular morphology and reductions in CBF, where it has been found that risk factors for vascular diseases, such as high blood pressure and high cholesterol, are risk factors for AD as well (Farkas & Luiten, 2001; de la Torre, 2002; Iadecola,