NEW CONCEPT OF THE ETIOPATHOGENESIS OF LATE SPORADIC FORMS OF ALZHEIMER’S DISEASE
Alzheimer’s disease is the main cause of cognitive impairment in old age. The basis of neurodegeneration is the progressive death of neurons and glial elements. Alzheimer’s disease is characterized by the onset of the pathological process from the hippocampus and deep parts of the temporal lobes. At the heart of its pathogenesis, a significant role belongs to the proteins β-amyloid and τ-protein. However, the amyloid theory does not explain the initial stages of the disease, which remain unknown. In addition, the processes that contribute to an increase in the activity of β-secretase, which provides pathological posttranslational proteolysis of the precursor protein, are not completely clear. Also, the mechanism of sequential propagation of the neurodegeneration process to close, functionally related structures of the brain, the source of which is located in the hippocampus and deep parts of the temporal lobes, has not been studied. The proposed hypothesis aims to explain the development of these links in the pathogenesis of Alzheimer’s disease. It assumes the presence of the following main pathological blocks that consistently develop in the brain tissue of patients with Alzheimer’s disease: the formation of capillary insufficiency, the development of mitochondrial dysfunction and the process of slow excitotoxicity, disruption of the ubiquitin-mediated protein degradation system, activation of the β-secretase pathway of APP proteolysis, prion-like protein proliferation β-amyloid. A major role is assigned to the disruption of the ubiquitin-mediated protein degradation system, which manifests itself in the conditions of ischemic damage under the influence of excitotoxicity processes. In addition, the prion-like properties of the protein β-amyloid play a significant role. Our assumption, at present, is largely theoretical in nature and needs to be confirmed through experimental study and clinical observations (bibliography: 14 refs).