Etiology and Pathogenesis of Alzheimer’s disease

Alzheimers disease is a degenerative brain disturbance and is the main cause of dementia. The major(ip) clinical manifestations of Alzheimers disease embarrass gradual overtaking of memory and language. Other major symptoms and signs of this disease argon psychiatrical and behavioral abnormalities and disabilities in the r break throughine or daily living activities.The aetiology and Pathogenesis of Alzheimers disease include various factors. Biological Factors Even though the etiology and wayogenesis of Alzheimers disease is still non known fully, it is discovered to involve a complex mix of transmitted as well as environmental factors.Among genetic and environmental factors, genetic factor is proved to be playing a major role in the etiology and pathogenesis of Alzheimers disease. The most important cause of Alzheimers disease is put together to be the mutations in chromosomes 21, 14 and 1 which are spread or moved in a characteristic autosomal dominant mode. These mutat ions make protein overproduction in neuritic plaques, B amyloid. Even though the beginning of the familial form is often early, the nature and r extincte of the ail is found to be influenced by few environmental factors.But it is found out that familial form is responsible for only a negligible proportion of cases of Alzheimers disease (even less than five percent) (Cummings et al. , 1998b). Nearly fifty percent of the people who are having ancestors with Alzheimers disease are found to be getting this put out once they enter their 80s and 90s (Mohs et al. , 1987). Few genotypes (the model of genetic inheritance in a persons automobile trunk) are found to give risk for the late-onrush Alzheimers disease (which is very common).Taking an example, the ApoE-e4 allele on chromosome 19, that encourages the deposition of B amyloid, is proved to increase the risk for developing Alzheimers disease (Corder et al. , 1993). All other genes that are doubted to be responsible for the developme nt of Alzheimers disorder are being studied (Kang et al. , 1997). Apart from this particular reason, there are various other biologic risk factors that contribute to the development of Alzheimers disorder Cummings et al. , 1998b).Cognitive capabilities and aging are among the biological factors. The manner in which these traits contribute to the increased risk is not still proved, however, it is proved in the medical field that the numerous neurobiologic changes that are associated with the normal aging of the brain of a person also contribute to the major risk factors of Alzheimers disorder. As people get into the later part of their life, this age related neurobiologic changes make then more liable for Alzheimers disorder.These neurobiologic changes include neuron and synaptic loss, lessened dendritic intersect, reduced size and density of neurons present in the nucleus basalis of Meynert, and poor cortical acetylcholine take aims (Cummings et al. , 1998b). Based on these facto rs and the frequence and occurrence curve of this disorder, medical researchers founder come to the conclusion that people are very much liable to Alzheimers disorder if their life span is extended (beyond the normal age) beyond eighties and nineties (up to 100 and 150). People above 90 years are highly susceptible to Alzheimers disorder.Among this, those who have Alzheimers history in their family are 90 % prone to this disorder. Protective Factors Apart from the biological factors there are various other factors that influence the trespass of Alzheimers disease. Various protective factors that are powerful enough to delay the commencement of Alzheimers disorder have been discovered. For example, Genetic endowment with the ApoE-e2 allele is capable of reducing the risk of Alzheimers disorder (Duara et al. , 1996). The exact role and the original mechanism of action of ApoE-e2 allele, however, are not totally understood.Deep thinking, higher educational level and wisdom are als o proved to be associated with the delay in the commencement of Alzheimers disease (Stern et al. , 1994 Callahan et al. , 1996a). Few medication and drugs are also found to be good for delaying the blast of Alzheimers disorder. For example, medications, like nonsteroidal anti-instigative drugs (Andersen et al. , 1995 McGeer et al. , 1996) and estrogen replacement therapy (Paganini-Hill & Henderson, 1994), are found to be effectively delaying the commencement of Alzheimers disease.Apart from this, Vitamin E and the drug selegiline (otherwise known as deprenyl) are also proved to holdup the crucial stages of the course of Alzheimers disorder, for example the nursing home placement, near functional impairments or disorders as the disease progresses and lead to death (Sano et al. , 1997). According to Behl et al. , 1995, the course of action of the protective agents in a person is not completely known however, these agents are proved to check the toxic action of oxidative stress (thr ough antioxidants like vitamin E or estrogen).These agents also counter the work of seditious mediators related to plaque formation (through anti-inflammatories) (Mark et al. , 1995). Hi barathology The pathophysiology of Alzheimers disorder is also proved to be associated with the histopathologic variations in Alzheimers disease. These histopathologic changes include neuritic plaques, synaptic loss, neurofibrillary tangles, hippocampal granulovacuolar degeneration, and B amyloid angiopathy (Cummings et al. , 1998b).Majority of the genetic and epigenetic risk factors are some or the other way linked with B amyloid. This has helped the medical researchers to conclude that the formation of B amyloid peptide is the most crucial pathological event or step in the course of spread of Alzheimers disorder in a person (Cummings et al. , 1998b Hardy & Higgins, 1992). A successful intervention in the course of Alzheimers disease spreading may include get in the way of any of the numerous st eps include in the slow progress of Alzheimers disease pathogenetic cascade.Few of the intervention modes include step in to reduce B amyloid generation from the amyloid precursor protein, intervening to decrease the B amyloid aggregation as well as the generation of beta-pleated sheets, and intervening in the amyloid-related neurotoxicity play. Successful interference in these steps may help interrupt Alzheimers spread. Apart from this, few therapies can successfully block the neuronal cellular phone death and can slow down the inflammatory response occurring in neurotic plaques.Therapies are also proved to inhibit the work of certain growth factors and hormones and also delay the replenishment of deficient neurotransmitters. As the complete obstruction of the processes within the B amyloid cascade may affect the usual cerebral metabolic processes, successful interruptions may bring close partial interruptions (Cummings & Jeste, 1999). Studies about the molecular neuroscience o f Alzheimers disease have researched several crucial aspects of pathophysiology and etiology.Researchers are working to thoroughly understand the entire processes and reasons behind cell death, neuronal degeneration and subsequent memory degradation. Medical world is expecting new revelations from these studies and are on the way to lay a new therapeutic path for eliminating Alzheimers disease from the world (National Institute on Aging, 1996). Medical world is expecting researchers to come out with the real physiological factor that makes a human ashes prone to Alzheimers syndrome. Role of AcetylcholineAcetylcholine is also suspected to play a part in encouraging Alzheimers disorder in a person. way out or decrease of the neurotransmitter acetylcholine also is proved to be responsible for the pathogenesis of Alzheimers disease. Postmortem researches in Alzheimers disease infected people have explained the loss or reduction of basal forebrain and cortical cholinergic neurons and t he exhaustion of choline acetyltransferase, which is the enzyme that carry out acetylcholine synthesis (Mesulam, 1996). Several post mortem reports have come out with the same reason.The scale of this central cholinergic deficit is associated with the severity of dementia that results in the cholinergic hypotheses of cognitive deficits in Alzheimers disorder (Mesulam, 1996). This hypothesis and the clinical researches have proved that Acetylcholine play a major role in Alzheimers disease. However, acetylcholine is not the only neurotransmitter that encourages the growth of Alzheimers disorder in a patient. Researchers are still working to find out the role of other substances in the pathogenesis of the Alzheimers disorder.The researches related to the pharmacological treatment of this syndrome are coming out with new results. It has been proved that a delay or break in the spread of Alzheimers disease is proved to reduce its prevalence in the body of a patient even by half (Breitner , 1991). In order to inhibit the spread of this syndrome in a person it is necessary to delay the onset of the disease to such an extent where mortality from other resources surpasses the frequency of the steps of the disease.So the most crucial step in inhibiting Alzheimers disease is the identification of the factors that stop the onset or slow down the progress of the disease in the patient. Working on these agents would help reduce the spread of the disease. 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