Diseases that cause neural degeneration include those that cause cell death and cause the degeneration of nerve tissue. Alzheimer’s disease, the most prevalent form of dementia, is the most prevalent neurodegenerative condition. Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis are a few more frequent degenerative illnesses. It is yet unknown what causes neuronal death in neurodegenerative disorders. However, this illness is linked to several hereditary and environmental variables. The population’s increasing life expectancy, which has expanded significantly in recent decades, is one of the major risk factors.
Consequently, neurodegenerative disorders will continue to spread in the future. Neurodegenerative illnesses exhibit different symptoms depending on which part of the CNS is impacted. Amyotrophic lateral sclerosis patients have cerebral cortical degeneration, mostly resulting in cognitive-behavioral issues. Parkinson’s disease affects the dopaminergic cells of the substantia nigra, which are essential for the healthy operation of the cortical-subcortical circuits that control movement. The disruptions in this situation are mostly of a motor origin.
The neurotrophin family of structurally similar polypeptide growth factors includes brain-derived neurotrophic factors. After BDNF’s extraction from a brain extract, which supported neurons resistant to the effects of nerve growth factor, it was initially characterized in 1987 (Rao et al., 2019). The BDNF gene produces the protein BDNF, which has a molecular weight of 13.5 kDa and 119 non-glycosylated amino acids (Merkouris, 2020). In order for the nervous system to develop properly and continue to operate normally in an adult organism, BDNF is crucial.
The results of a new study have been published that still confirms neurogenesis in adults. Moreover, to this study’s authors, the neuronal formation rate does not decrease with age (Jia et al., 2020). This discovery may be able to find a cure for many age-related brain diseases, from Alzheimer’s to psychiatric problems. The experts studied the hippocampus of 28 men and women between the ages of 14 and 79 (Jia et al., 2020). Using a wide range of techniques and technologies, the team examined the formation of new blood vessels and the volume and number of nerve cells in the brains of people of different ages.
Not the entire brain was studied, but only an organoid called the dentate fascia of the hippocampus. Previously, it was thought that neurogenesis was possible here and in the olfactory bulb and cerebellum. Brain cells were studied within hours of these people’s deaths (Parnia et al., 2022). What is known about the people whose brains were studied is that they were healthy before they died. At the same time, in people with Alzheimer’s disease, the intensity of new neuron growth is reduced.
The biological factors of depression include specific disorders of neurochemical processes (metabolism of neurotransmitters such as serotonin, noradrenaline, and acetylcholine). These disorders, in turn, may be hereditary. Depressive symptoms in non-psychotic patients may develop as a consequence of the patient’s personality response to an existing somatic illness or as somatization of the primary depressive disorder (somatized depression). Depression leads to impaired neuroplasticity, which possibly serves as a basis for chronicity of the process and development of cognitive deficit. This may explain Miranda’s symptoms of depression.
The revealed disorders of neurotrophic factors in depression make neurotrophic drugs appropriate for patients, but further research into the possibilities of neurotrophic therapy for depression is necessary. Antidepressants protect the hippocampus from neuronal loss and make the stress-induced atrophic changes reversible, which supports the neurotrophic theory of depression. However, it is unclear what other brain regions also alter neuroplasticity in response to antidepressant therapy. Studies on the postmortem brains of depressed suicide victims have revealed a drop in BDNF levels in the hippocampus (Misztak et al., 2020). Antidepressants and electroconvulsive treatment increase the synthesis of BDNF and growth hormone.
Stress, neurogenesis, and hippocampus shrinkage in depression may all be connected via BDNF. However, research on BDNF gene polymorphism did not find any correlation with depression (Kishi et al., 2018). BDNF has a non-specific role in several mental disorders. Although blocking the BDNF gene in mice does not have the same effect as depression, it may lessen the impact of an antidepressant (Castrén & Monteggia, 2021). Additionally, raising BDNF levels in the brain are several neurotoxins and inflammatory processes. Antidepressants can promote the growth of new synapses, which helps the brain process external stimuli more effectively; most alter the expression of BDNF.
Correction of cognitive disorders is paramount for normalizing patients’ daily functioning when remission is achieved, particularly restoring the impaired ability to work. According to a survey of patients diagnosed with depression, they feel difficulty concentrating and decreased mental performance almost all the time (Son et al., 2020). Furthermore, despite normalizing the emotional state during remission, patients often experience cognitive difficulties, which interfere with work and daily life. These data confirm the autonomy of cognitive impairment, which should be considered when choosing a treatment tactic for depression. Thus, achieving a satisfactory level of daily functioning is impossible without restoring the patient’s normal level of mental performance, without additional influence on the cognitive component. This symptom is observed in Miranda; she has difficulty focusing on what is happening, so she gets lost in her native neighborhood.
The protein encoded by APOE4 has an altered functional activity and is found in Miranda. The APOE4 polymorphic allele of the APOE gene is a major genetic risk factor for Alzheimer’s disease, increasing the disease’s probability by more than 3-fold (Jabeen et al., 2022). The mechanisms contributing to the earlier development of neurodegeneration in polymorphism carriers are associated with several factors, including impaired lipid metabolism in the CNS, predisposition to the formation of neurotoxic amyloid-beta oligomers, delayed clearance of amyloid-beta from the CNS, and impaired regulation of immune processes in the CNS. Experiments on transgenic animals predisposed to AD show that APOE4 carriage accelerates the formation of amyloid plaques and the development of dystrophy of the CNS parenchyma adjacent to the plaques (Parhizkar & Holtzman, 2022). In addition, as shown in mice, in the presence of the APOE4 allele, amyloid plaques tend to localize not in the parenchyma but in the vicinity of the arteriolar walls.
Formation of a complex with ApoE promotes clearance of extracellular amyloid by facilitating its endocytosis by microglia and CNS astrocytes through the interaction of ApoE with membrane scavenger receptors LRP1. Alzheimer’s disease is a neurocognitive disorder that is the most common cause of dementia; it causes 60 to 80% of dementia in older adults (Dumurgier & Sabia, 2021). In the United States, it is estimated that 10% of people over the age of 65 and suffering from Alzheimer’s disease (Alzheimer’s Association, 2018). Most cases of Alzheimer’s disease are sporadic, with late-onset and unspecified etiology. The age of the patients best predicts the risk of developing the disease.
Thus, Miranda is a 79-year-old woman, so she is at risk for Alzheimer’s disease. Her symptoms are similar to those of this disorder. Because she has the APOEe4 gene, the risk of Alzheimer’s disease, and therefore dementia, increases in the woman. The woman forgets the names of loved ones, has difficulty navigating in familiar surroundings, and her lifestyle and the traumatic experience of the death of her husband explain her depressive state.
References
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