Cerebral Amyloid Angiopathy Samples †MyAssignmenthelp.com

Question: Discuss about the Cerebral Amyloid Angiopathy. Answer: Introduction Cerebral amyloid angiopathy has been referred to as congiphilic angiopathy, which is a form of angiopathy characterised by deposits of blood vessel walls in the blood nerval system, which shows the presence of abnormal of amyloid in the brain tissue, (Liu, et al., 2016). CAA has been associated with Alzheimers disease, which leads to bleeding of the brain which is often associated with dementia. The bleeding is often associated with bleeding of the lobe, (Walton et al., 2015). It often occurs through sporadic occurrence among the elderly population. CAA often has been categorized into two; Iceland and the British type. Medical management is to manage the symptoms. Speech and physical therapist have played significant role in managing the disease. Cystatin protein has often been associated with brain medical condition and plays crucial role in brain disorders. Cystatin gene is encoded with initial CST3 gene used as a biomaker, (Wuttkle et al., 2015). It has been associated with brain disorders. Mutations of the cystatin gene has been associated with cerebral amyloid angiopathy, it forms the basic susceptibility in causing Alzheimers disease, (Vella, 2015). The Gene Gene function and expression Cystatin gene is a protein form that encodes itself to humans to form CSTA gene. The gene forms super family forms like the sequences which form the normal cystatin like sequence which are active producing protease inhibitors. Some of the sequence often loses its inhibitory effect. Inhibitory families forms three groups which include the cystatin also referred to as stefins, type two cystatin and the kinigogens. The gene encodes the gene stefin which functions as cystatin protease inhibitor which forms the complex compound with papain and cathepsins B, H and L. They functions as a precursor of cell envelopes which are cornified in the keratinocytes and plays a role in epidermal development and maintenance, (Redecke et al., 2013). Gene structure Complete amino sequence of single polypeptide of human cystatin corresponds to the C DNA. The three characteristic structure of cystatin C is similar to homologous protein chicken cystatin. Studies have shown that the truncated form of cystatin C (A8) and of cystatin C variants produced at site directed mutagenesis. Of B18, H5, H6,L12, M7 and also identification of sequence of similarities of cystatin which have properties of peptide segments. Cystatin protease inhibitor, cystatin C forms amyloid deposits which accumulate in the cerebral haemorrhages with the amyloidosis Icelandic type, which leads to haemorrhages, (Xu et al., 2014). Cystatin is also associated with neurological a degenerative disease which is involved in pathogenic processes leading to amyloid deposits in the cerebral vasculature which is a condition which leads to cerebral haemorrhage in older patients. Gene locus Cystatin gene locus and conservation usefulness in animal models with the protein inhibitor has been found as expression of two sequence tags. The gene has been found to be located in the 2G3 chromosome area; it encodes the entire 141 amino acids. The protein has been found to be related to family 2 cystatins which lacks critical consensus sites for inhibition. The characteristics have been found in male reproductive system in mouse, (Miller et al., 2017). The protein Protein fucntion The protein nature of the cystatin C is non glycosylated basic protein which is a member of the cystatin super family of protease inhibitors. The structure is often illustrated with promotion and determined by the gene. The low molecular gene is in stable concentration of the protein which is determined by the glomerular filtrate rate of the individual. Protein description Cystatin C is a protein encoded with the form of CST3 gene which is mainly used as biomarker for kidney function. However more recent research has linked its role in predicting new onset or deteriorating cardiovascular disease. It also plays a significant orle on the brain disorders which often involves the amyloid protein. In humans, cells with nucleus produce cystatin C which produces chain of 120 amino acids. It fuses itself in the tissues and body fluids and acts as protein inhibitor, (Teyssou et al., 2013). Its molecular biology entails the super family proteins that contain the multiple cystatin like consequences. These members are active cystatin protease inhibitors while others have no inhibitory effects. The three inhibitory families include the type 1 cystatin proteins, type two cystatin and the kinogens. The type two are often associated with human fluids and secretions, where they appear to provide protective functions. Protein Properties The cystatin proteins are the class of cystatin proteins which are found in variety of human beings fluids, secretions. The gene is often found in the cystatin locus on the chromosome 20 which contains the majority of type two cystatin genes. It is encoded in the in extracellular inhibitor which is found in all organs. According to Akerblom et al., (2014), the CST3 gene contains the cystatin locus and comprises of 3 exons which have the coding regions and non coding regions in the gene. It contains the most extracellular inhibitor of cystatin protease. It is found highly in biological fluids and expressed in all organs of the human body. The three polymorphism in the promoter region lead to two variant. Cystatin C is a non glycosylated basic protein at the Ph of 9.3. The crystal structure of cystatin c is characterized by the short alpha helix and long helix alpha which is found across large anti parallel stranded beta sheet. Cystatin C forms dimmers which by exchanging the sub domains in the paired state. Cystatin C has been measured to having random sample of serum blood with red blood cells and clotting factors have been eliminated using immunoassays like the nephelometry. The test have proven to be more expensive to run Protein dysfunction and analysis Cystatin gene has been associated with neurologic disorders. A mutation in the cystatin 3 gene is responsible for the Icelander hereditary disease. It is a condition which predisposes the intracellular hemorrhage, stroke and other related diseases. These diseases are inheritable. It binds s the amyloidal b and leads to reduction of the aggregation and deposition. It is a potential target for Alzheimers diseases. These mutations have often been associated with amyloidal angiopathy. Majority of the studies done have majored on the CST3 Role of susceptibility in Alzheimers disease, (Wisment et al., 2015). Protein expression in the vascular wall of the smooth muscle proteins is often severely reduces in both atherosclerotic state and the aneurismal aortic lesions which is clearly observed in the aortic disease. The protein further has been shown to have antimicrobial effects which inhibit the replication of herpes simplex virus. Serum cystatin c is often measure with automated immunoassay. More sensitive changes of the GFR serum creatinin if often associated, (Stewart et al., 2014). The disease Description of the disease The cerebral amyloid angiopathy refers to the accumulation of the beta amyloid in the medial adventitia of the small and midsized arteries of the cerebral cortex and the lepromeninges. It is a factor of disorder in which the amyloid is deposited in the brain and is not linked to systemic amyloidal. CAA has always referred to one of the morphologic hallmarks of the Alzheimers disease. it is found in brains of the elderly people whose health state of the neurology is okay, (2-3). It is often asymptomatic; however it may lead to dementia, intracranial haemorrhage or transient events. The diagnostic guidelines of the disease have been clarified with the cerebral amyloid angiopathy, which associates the CAA with intracranial haemorrhage. The fouls levels of certainty in the diagnosis of the CAA are often considered as definite, probable supporting pathogenic evidence Molecular and cellular analysis The definite form of the CAA involves the full post-mortem examination which often reveals the lobar , cortical or the cortical sub cortical haemorrhage of severe case of CAA. Probable CAA has been found with supporting pathologic evidence. The clinical data of the pathologic tissue shows the haemorrhage of the characteristics and degree of amyloid deposition. The probable CAA shows the clinical data and magnetic resonance imaging which shows the multiple haematosis among patients over the age of 60 years. The aetiology of the disease often occurs in sporadic form. However genetic predispositions often exist, which include apoli protein subtypes which confer with different risk profiles. Most of the case of CAA is related with the intracranial haemorrhage which is spontaneous. Evidence have often linked data which suggest that the amyloid is produced in responds to the smooth muscle cells of the tunica media which damages the vessel walls, (Bai et al., 2016). Amyloid deposition is often complex and involves the key process of production of amyloid precursor proteins, processing of precursor proteins, aggregation of proteins and the fibrial formation. The impaired formation and accumulation of the soluble and the insoluble beta amyloid peptides have often underlie the occurrence of CAA shows the association between CAA and the Alzheimers disease. Amyloid fibrials often deposits itself in the cerebral vessels like in the case of amyloid CAA and plaques the parenchyma part of the brain, (Fitzpatrick et al., 2013). The accumulation dynamics of the clearance of the amyloid can be related to the impaired drainage from the peri- vascular basement membranes. The intestinal fluid and solute drain form the brain and the cervical lymph nodes in the capillary basements and the brain are powered by the pulsatile flow in the vessel, (5). The aetiology of the disease forms the basis of the hereditary brain cerebral haemorrhage with amyloidosis. The Dutch type hereditary cerebral haemorrhage with amyloidosis is often a disorder with complete penetration. Among individuals having this, 87 % have been found with ICH and 13% have infarcts. The amyloids have been in the cortical and leptimenngineal vessels; parenchyma neurofibrialliary which are not seen. The Icelandic type hereditary celebral haemorrhage has also shown autosomal dominant. The presences of the patient in the first episode of ICH in the third or fourth decade in some patients have shown underage clinical symptoms as young as age of 15 years. Amyloid angiopathy is more wide spread in this type than others which often involve arteries in the cerebrum, cerebellum and the brainstem part of the brain. The amyloid protein has shown itself as mutant gene of the cystatin protease inhibitor of cystatin C, (Carare et al., 2013). The haemorrhage in the protein has often been observed as the media for damages and the adventia of cortical and leptomengeal vessels which often leads to the thickening of the basal membrane. This process often results in the fibrinoid necrosis and the micro aneuryims formation which predisposes it to haemorrhage. The CAA has always been linked to the changes in the brain which include the lobar cerebral and the cerebella haemorrhage, leuko encephalopathy and plague depositions. It is often associated with the hypo-perfusion. Neuro pathology has been linked to mild CAA which affects the relatively smaller portions of the leptomengeal and superficial cortical vessels. Complete erosion of the arteries often occurs with only the endothelium surrounding the deposit remaining, which predisposes to haemorrhage. When viewed under electron microscope, it demonstrates the fibrils of the amyloid in the outer basement membrane in the initial stage of the CAA, (Boyle et al., 2015). Current and future treatment options More prevalence has been observed among the women more than men, with over the age of 65 years with risks increasing as the age advances. Patients with amyloid angiopathy of the cerebral often have increased risks of bleeding while taking medication such as the warfarin even when administered within the level of anticoagulation range. The vasculopathic change often predisposes these patients to small bleeds. The use of anticoagulant results in the enlargement of small haemorrhages what would otherwise remain asymptomatic. Withdrawing from these drugs of the family of anticoagulant agents has been shown to be prudent intervention to prevent the occurrence of patients with prior lobar haemorrhages. Strong evidence which provides the link between the CAA and the antithrombotic therapy is not sufficient. Treatment of hypertensions has been found to promote prevention of the recurrence of haemorrhage in the CAA. Transplantation has always been associated with the hereditary cause of CAA, mortality and the occurrence of cerebral haemorrhage and the dementia among patients who had transplants. This study could not be generalized due to the small sample size it targeted, (Mattila et al., 2014). The medical process of cerebral amyloid angiopathy is untreatable, thus management of CAA related intracranial haemorrhage has been found to be identical to the standard management of CH. Cerebral drug developed for the managed of the CAA to reduce the amyloid formation and deposition has not been widely utilised due to safety concern. References kerblom, A., Eriksson, N., Wallentin, L., Siegbahn, A., Barratt, B.J., Becker, R.C., Budaj, A., Himmelmann, A., Husted, S., Storey, R.F. and Johansson, ., 2014. Polymorphism of the cystatin C gene in patients with acute coronary syndromes: Results from the PLATelet inhibition and patient Outcomes study. American heart journal, 168(1), pp.96-102. Bai, H. X., Zhou, H., Tan, X., Huang, X., Yang, L. 2016. Cerebral amyloid angiopathy as an etiology for cortical superficial siderosis: an unproven hypothesis. American Journal of Neuroradiology, 37(3), E25-E25. Boyle, P. A., Yu, L., Nag, S., Leurgans, S., Wilson, R. S., Bennett, D. A., Schneider, J. A. 2015. Cerebral amyloid angiopathy and cognitive outcomes in community-based older persons. Neurology, 85(22), 1930-1936. Carare, R. O., Hawkes, C. A., Jeffrey, M., Kalaria, R. N., Weller, R. O. 2013. cerebral amyloid angiopathy, prion angiopathy, CADASIL and the spectrum of protein elimination failure angiopathies (PEFA) in neurodegenerative disease with a focus on therapy. Neuropathology and applied neurobiology, 39(6), 593-611. Fitzpatrick, A. W., Debelouchina, G. T., Bayro, M. J., Clare, D. K., Caporini, M. A., Bajaj, V. S., ... MacPhee, C. E. 2013. Atomic structure and hierarchical assembly of a cross- amyloid fibril. Proceedings of the National Academy of Sciences, 110(14), 5468-5473. Liu, C. C., Zhao, N., Yamaguchi, Y., Cirrito, J. R., Kanekiyo, T., Holtzman, D. M., Bu, G. 2016. Neuronal heparan sulfates promote amyloid pathology by modulating brain amyloid- clearance and aggregation in Alzheimers disease. Science translational medicine, 8(332), 332ra44-332ra44. Mattila, O. S., Sairanen, T., Laakso, E., Paetau, A., Tanskanen, M., Lindsberg, P. J. 2014. Cerebral amyloid angiopathy related hemorrhage after stroke thrombolysis: Case report and. Redecke, L., Nass, K., DePonte, D. P., White, T. A., Rehders, D., Barty, A., ... Williams, G. J. 2013. Natively inhibited Trypanosoma brucei cathepsin B structure determined by using an X-ray laser. Science, 339(6116), 227-230. Stewart, G. D., OMahony, F. C., Laird, A., Rashid, S., Martin, S. A., Eory, L., ... Mullen, P. 2014. Carbonic anhydrase 9 expression increases with vascular endothelial growth factortargeted therapy and is predictive of outcome in metastatic clear cell renal cancer. European urology, 66(5), 956-963. Teyssou, E., Takeda, T., Lebon, V., Boille, S., Doukour, B., Bataillon, G., ... Salachas, F. 2013. Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology. Acta neuropathologica, 125(4), 511-522. Walton, E., Hass, J., Liu, J., Roffman, J. L., Bernardoni, F., Roessner, V., ... Ehrlich, S. 2015. Correspondence of DNA methylation between blood and brain tissue and its application to schizophrenia research. Schizophrenia bulletin, 42(2), 406-414. Wiseman, F. K., Al-Janabi, T., Hardy, J., Karmiloff-Smith, A., Nizetic, D., Tybulewicz, V. L., ... Strydom, A. 2015. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome. Nature reviews. Neuroscience, 16(9), 564. Wuttke, M., Schaefer, F., Wong, C. S., Kttgen, A. 2015. Genome-wide association studies in nephrology: using known associations for data checks. American Journal of Kidney Diseases, 65(2), 217-222. Xu, Y., Lindemann, P., Vega-Ramos, J., Zhang, J. G., Villadangos, J. A. 2014. Developmental regulation of synthesis and dimerization of the amyloidogenic protease inhibitor cystatin C in the hematopoietic system. Journal of Biological Chemistry, 289(14), 9730-9740.