Genetic and neurologic causes of Alzheimer’s disorder
Alzheimer’s disorder is a genetic and neurologic disorder in which brain cells die, causing the brain to shrink. The occurrence of the disorder results in continuous loss of thinking and behaviour skills of the people. The function independent ability of the brain function is highly affected, that symptomized as a language problem, unpredictable behaviour and the permanent loss of memory. Glial cells of the brain tend to surround the neurons to maintain their activities by protecting the neurons from physical and chemical damage. However, disease occurrence leads to the destruction of glial cells, creating plaque formation, which is considered Alzheimer disorder or AD. The disease is directly related to the interrupted nervous system connection in which nerve cells do not sensitize the signals to be actively involved for the particular actions (McKhann et al., 2011). The further discussion will reflect the genetic alteration, brain parts associated with disease, neuroanatomy, history, pathophysiology, and detection of disease.
Brain is the central portion of the nervous system, which is composed of more than 10 billion neuron specialized cells. All the nerve cells either enter into brain or exit from brain carrying electrical and chemical signals throughout the body. However, various neuronal abnormalities in performing brain functions are associated with causing the disease. The mutation in any nerve cells in the brain can lead to non-functionality or accumulated function of the nerve cells, making the corrective cells be non-functional or altered in roles (McKhann et al., 2011).
The disease has been extremely prolific over the few last decades. 10 genes associated with disease are identified from different chromosomes, ch-21, ch-23, and ch-24, out of which 4 genes, namely APP, PSEN1, PSEN2, and APOE are specific. The mutation in these genes leads to neuropsychiatric disorders (Bertram & Tanzi, 2004). The disease is also considered a neurogenerative disease because of alteration of the neuronal protein processing in which amyloid-beta and tau protein play a crucial role in removing cell debris. However, the mutation in these two proteins can lead to the occurrence of the disorder. The mutated amyloid protein plaque forms through the degenerative processes of axonal, dendritic, and astrocytes, which further alter the activities of two main enzymes named kinase and phosphatase. The alteration in the enzymes leads to tau protein hyperphosphorylation., which is a cause of tangles formation. Tau proteins which are responsible for microtubule stabilization, get affected due to the mutation caused in dephosphorylating enzymes (Iqbal et al., 2005)
The important glial cell is named microglia, which not only clears the cell debris but also remove the beta-amyloid plaques. The functions of microglia are controlled under the toll-like receptors of the immune system. Microglia remain in collaboration with the blood vessels to regulate the delicate balance of neurons to maintain the proper functioning of brain. The glial cells, which are involveed in cleaning the debris from brain, get inflammation, which makes the glial cells fail to destroy the wastes, which can also result in causing Alzheimer disease (Pizza et al., 2011).
The disease is associated with the destruction of the brain neurons that are connected with the brain signalling, involved in memory from entorhinal cortex, hippocampus and cerebral cortex.
- Hippocampusis the temporal lobe of the brain, which helps in understanding, remembering, and recognizing face, voice and objects. Occurrence of Alzheimer disorder starts from this lobe of the brain. Because of accumulation of several kinds of molecular forms, which are composed through the breakdown of beta-amyloid protein. The abnormality of the occurred protein clump forms a plaque disrupting the cell function leading to disease. Another kind of protein abnormality is called neurofibrillary tangles (also called tau). The accumulation of tau or abnormal chemical changes in tau leads to detaching from the microtubules disrupting the functions of tau that tend to block the transport system and hence harms the synaptic communication of the neurons. The amyloid-beta and tau protein accumulation (due to mutation) results in damaging nerve cells to make the hippocampus non-functional. The proliferation of the mutated proteins gradually spreads all over, affecting a large portion of the brain by destroying all nerve cells (Kovács, 2022).
- Entorhinal cortexis the portion of the medial temporal lobe from which information enters or exits from the destination of hippocampus. Thus, the lobe is considered as the information pathway, which is essential to store memories. The alteration in the switch genes present in the in’s entorhinal cortex can cause the incidence of Alzheimer disorder to increase, making the other genes functionless for normal cell proliferation. However, the accumulation of uncontrolled growth of the switch genes is involved in inflammation, oestrogen signalling., phospholipase D, and activation of the platelets (Bottero et al., 2021)
- The cerebral cortexis the portion of the brain which is associated with regulated behaviour, language, social skills and reasoning. The adverse effects of Alzheimer’s disorder result in the cerebral cortex’s functions being affected, which are connected with brain signalling, such as communication, metabolism and repair (Kovács, 2022).
Brain parts associated with Alzheimer’s disorder
Alzheimer disease occurs due to the accumulation of beta-amyloid and neurofibrillary tangles that occur in the brain portions called cerebral cortex and hypothalamus. The condition leads to gradual cognitive deterioration. The chemicals carrying signals from neurons are called neurotransmitters (type of hormones). The neurotransmitters play a vital role in cell functioning by transmitting signals from brain to cells and cells to brain. Acetylcholine and glutamate are two primary responsible neurotransmitters transmitting signals to activate muscles for arousal, providing memory, learning and balancing abilities. However, in conditions of occurrence of AD, the stimulation of plaque and tangles formation takes place. Because plaque accumulation in the neurons make the activity of neurotransmitters either increase or decrease, leading to the breaking down of the signalling process. Gradually brain cells become excitotoxic because of loss of functions and ultimately die (Dani & Bertrand, 2007).
AD is the concerning future health care challenges on the global parameter that is affecting the age of people dominantly. The increased prevalence of AD occurrence is observed in developed as well as in developing countries. AD is considered a type of dementia disorder that is associated with multiple cognitive problems in patients as estimated number of identified AD cases worldwide was recorded in the year 2010, carrying more than 35 million people suffering from AD. However, the expected range of AD patients by 2050 is 150 million. AD is characterized by the reversible deterioration of the cognitive functions of 4rhe people leading to various difficulties in balance, thinking, reading and writing. The AD diagnosis reports provide the data that patients who suffer from AD have a range of diseased life of 5-12 years? (Huang et al., 2021).
The first arrival of AD was observed a century ago, in 1907, in which a 51-year-old woman named Auguste Deter showed the symptoms of loss of memory and impaired behaviour. The women were not able to memorize, read and write correctly. The signs were firstly described by the doctor Alois Alzheimer. The scientist used a sliver staining technique to observe the brain of a patient after her death. In the silver staining technique, various neurofibrillary tangles, amyloid angiopathy and neuritic plaques were seen to be formed. The scientist became famous for the research purpose due to the discovery of plaque structured illness released as neuropsychological consequences of disease in the year 1980. Hence, the disorder after its discovery by Alois Alzheimer was named Alzheimer’s disorder (Bondi et al., 2017).
Pathophysiology includes the formation of extracellular beta-amyloid plaques and Intracellular neurofibrillary tangles. The appearance of tangles and plaques result in synapsis loss of neurons that initiate from the temporal lobe, causes inflammation in brain and ends with neuronal cell death. The same clinical symptoms correlates with the other disorder named dementia (Dement, 2016). The widespread manifestations observed in the patients are impaired reasoning, language dysfunction, short-term memory loss, misplacing objects, poor judgment, language and visuospatial dysfunctions and behaviour disorders.
The epidemiology of AD has made the disease a concern of greater attention for the public and national AD research centre program (NADRC). NADRC program refined the study about the cause of neuropathy condition of Ads that disorders and impairments are characterized by forgetfulness, slowing through processes, depression and altered personal apathy. Similar cognitive impairments can be seen in subcortical dementia and Huntington’s disease. Several molecular changes take place in the brain tissues, which can be observed through the microscope. Some of the characteristic features such as imaging tests (Neuroimaging such as MRI and CT scan), clinical laboratory tests such as thyroid-stimulating hormone, vitamin B12 levels and physical examination of formal mental status tend to identify the disorder. For example, elevated levels of tau proteins can be detected through PET imaging, in which radioactive elements tend to bind with tau proteins. PET imaging that uses fluorodeoxyglucose or FDG is used to identify the decreased level of cerebral metabolism. Other test includes MRI, which determine the local atrophy in the temporal lobe and cortex (Chetelat et al., 2020).
Detection and diagnosis of Alzheimer’s disorder
The significant benefit in treating AD can be obtsined through the healthy diet rich in antioxidents, vitamins, proteins and minerals. For example, Citrus fruits can help in conformational changes in precursor of beta-amyloid preventing its mutation (Arslan et al., 2020). The incresased dietry potassium will delay aging porcess as higher AD cases are seen in elder people. The compounds present in garlic show very effective pharmacotherapy wigth admirable benefits to brain functions and neuronal physioloy (Mathew & Biju, 2008).
Conclusion
The cases of the patients affected with Alzheimer’s disease is increasing in population, majorly in the aged population, which has affected millions of American people. The condition is associated with a decline in cognitive behaviour and neuropsychiatric symptoms because of the accumulation of tau and amyloid-beta proteins. The formation of plaques and tangles due to protein accumulation can be seen through autopsy. In the ADs diseases, firstly hippocampus and entorhinal cortex get affected, making the disabilities of people in learning, remembering, writing and recognizing things. After the disabilities caused in the hippocampus and entorhinal cortex, the next portion of brain called cerebral cortex becomes affected. The destruction of the entorhinal cortex tends to make difficulties in good talk, reasoning, and social behaviour. Various disorders are associated with impaired cognitive abilities in the patients. Various neuroimaging and clinical laboratory tests can help in detecting the plaques, which are supposed to cause Alzheimer disorder.
References
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