In recent decades the term dementia has penetrated all areas of human activity becoming common in all media reports and lay conversation. New Institutes and Programmes have recently been launched in various countries to improve current understanding of the underlying pathology at the cellular and molecular levels requiring deeper insight into genetic and epigenetic mechanisms, which control brain activity in health and disease. The main attention of researchers in the dementia field over the years has been focused on Alzheimer's disease (AD), which is a highly prevalent condition predominantly affecting aging adults but in rare familial cases also striking younger individuals. Studies of such rare cases have given insights into the role of the amyloid-precursor protein (APP) and presenilin (PS) genes in the pathogenesis of AD and the concept of the amyloid cascade has dominated AD research for several decades. It is now apparent that AD is a complex multifactorial disorder which involves a number of genetic, epigenetic and environmental components. Moreover, AD shares several symptomatic and morphological features with other neurodegenerative diseases such as Parkinson’s disease (PD), fronto-temporal dementia (FTD), dementia with Lewy bodies etc. and the second pathological hallmark of AD, the tau pathology, shared by other dementias, is now taking a more central stage.
Recent studies have revealed genetic pleiotropy in neurodegenerative diseases suggesting that most of these diseases have polygenic character with multiple loci contributing to increased disease risk and presenting mixed pathologies. Furthermore, epigenetic mechanisms provide a wide platform for adaptive editing of the genetic information as a consequence of environmental stress and aging, which, in turn, trigger pathogenesis. Epigenetics mechanisms are considered to play a central role in initiating sporadic forms of AD, FTD, amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases leading to dementia. The failure of all attempts to design a successful therapeutic approach for halting or reversing AD based on previous research might be explained by the incredible complexity of the underlying mechanisms and individual characteristics of patients. Each individual has a unique pattern of genetic and epigenetic characteristics with a highly specific complexity of genes, polymorphisms, mutations, RNAs, proteins, lipids and oligosaccharides, resulting in distinct genome, proteome, metabolome and, finally, their interactome identity. Modern techniques, collaborative consortia of scientists and adequate cohorts of patients at various stages of disease complemented by matching controls should provide a more complete picture of the molecular landscape initiating disease progression and manifestation. Original findings might lead to shifting current foci of research and change the way of thinking about dementia per se.
In this special issue we invite scientists from various fields of research to report their views, new data, animal models, methodological approaches and concepts for decoding the riddle hidden by nature deeply in the human genome and its developmental programme and finding where treatment can be applied to prevent and whenever possible to treat neurodegenerative diseases leading to dementia.
In recent decades the term dementia has penetrated all areas of human activity becoming common in all media reports and lay conversation. New Institutes and Programmes have recently been launched in various countries to improve current understanding of the underlying pathology at the cellular and molecular levels requiring deeper insight into genetic and epigenetic mechanisms, which control brain activity in health and disease. The main attention of researchers in the dementia field over the years has been focused on Alzheimer's disease (AD), which is a highly prevalent condition predominantly affecting aging adults but in rare familial cases also striking younger individuals. Studies of such rare cases have given insights into the role of the amyloid-precursor protein (APP) and presenilin (PS) genes in the pathogenesis of AD and the concept of the amyloid cascade has dominated AD research for several decades. It is now apparent that AD is a complex multifactorial disorder which involves a number of genetic, epigenetic and environmental components. Moreover, AD shares several symptomatic and morphological features with other neurodegenerative diseases such as Parkinson’s disease (PD), fronto-temporal dementia (FTD), dementia with Lewy bodies etc. and the second pathological hallmark of AD, the tau pathology, shared by other dementias, is now taking a more central stage.
Recent studies have revealed genetic pleiotropy in neurodegenerative diseases suggesting that most of these diseases have polygenic character with multiple loci contributing to increased disease risk and presenting mixed pathologies. Furthermore, epigenetic mechanisms provide a wide platform for adaptive editing of the genetic information as a consequence of environmental stress and aging, which, in turn, trigger pathogenesis. Epigenetics mechanisms are considered to play a central role in initiating sporadic forms of AD, FTD, amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases leading to dementia. The failure of all attempts to design a successful therapeutic approach for halting or reversing AD based on previous research might be explained by the incredible complexity of the underlying mechanisms and individual characteristics of patients. Each individual has a unique pattern of genetic and epigenetic characteristics with a highly specific complexity of genes, polymorphisms, mutations, RNAs, proteins, lipids and oligosaccharides, resulting in distinct genome, proteome, metabolome and, finally, their interactome identity. Modern techniques, collaborative consortia of scientists and adequate cohorts of patients at various stages of disease complemented by matching controls should provide a more complete picture of the molecular landscape initiating disease progression and manifestation. Original findings might lead to shifting current foci of research and change the way of thinking about dementia per se.
In this special issue we invite scientists from various fields of research to report their views, new data, animal models, methodological approaches and concepts for decoding the riddle hidden by nature deeply in the human genome and its developmental programme and finding where treatment can be applied to prevent and whenever possible to treat neurodegenerative diseases leading to dementia.
