Genomic and proteomic conversion of brain ischemia to Alzheimer's disease.

Despite many years of extensive research into the etiology and treatment of Alzheimer's disease, based on the importance of amyloid and tau protein as causative factors, these studies have stalled, have not brought any breakthroughs and, most importantly, have not led to any final conclusions. Therefore, the ineffectiveness of the above-mentioned actions and the pressure from the community of people affected by Alzheimer's disease forced the scientific community to change its way of thinking about the etiopathogenesis of this disease. This situation has prompted a group of scientists who have been studying the effects of brain ischemia for years to focus on post-ischemic changes, which-similarly to Alzheimer's disease-predominate in the hippocampus, leading to the development of amyloid plaques, neurofibrillary tangles and ultimately to dementia. In this context, it has been proposed that brain ischemia may play an important role in driving amyloid and tau protein pathology in the development of Alzheimer's disease. In this review, we present an update of extensive experimental and clinical studies conducted over several years on the role of brain ischemia in the neuropathogenesis of Alzheimer's disease. Current advances in understanding the ischemic etiology of Alzheimer's disease have revealed dysregulation of Alzheimer's disease-associated genes, including secretases, amyloid precursor protein, apoptosis, autophagy, mitophagy, tau protein, α-synuclein, apolipoproteins, LRP1, and RAGE. This article presents the relationship between genes which dysregulation is a result of brain ischemia and the cellular and tissue neuropathology characteristic of Alzheimer's disease and their proteins. These observations clearly indicate that, following brain ischemia, changes occur in the expression of Alzheimer's disease-associated genes and in the folding of disease-associated proteins such as amyloid, tau protein, and α-synuclein. This leads to massive neuronal death and disruption of the neuronal network, ultimately leading to the development of Alzheimer's disease-like dementia. Data indicate common genomic and proteomic factors in brain ischemia and Alzheimer's disease. It seems that the brain ischemia model may be useful in determining the role of folding proteins and their genes dysregulation in Alzheimer's disease. In the future, manipulation of genes and proteins associated with ischemia and ischemia-induced Alzheimer's disease will likely provide new hope for developing causal therapies that are urgently needed to prevent or treat Alzheimer's disease. The innovative/novel approach to the etiology of Alzheimer's disease presented in this review will provide stakeholders with a glimpse into the future.