Alzheimer’s Disease (AD) is a complex neurodegenerative disorder and the leading cause of dementia worldwide. Despite extensive research, the pathophysiology of AD remains incompletely understood, with multiple hypotheses proposed over the years. These include the amyloid beta (Aβ) and tau protein aggregation theories, inflammation, oxidative stress, metal ion deposition, genetic mutations, calcium signaling abnormalities, and mitochondrial dysfunction. While the Aβ plaque and tauopathy hypotheses have dominated the field, the repeated failure of drug trials targeting these pathways has raised doubts about their validity as therapeutic targets. This underscores the urgent need for a deeper understanding of the disease's multifactorial nature and the interactions between its various etiological factors. Recent studies have begun to explore these intricate interconnections, but significant gaps remain, particularly in elucidating the mechanistic links between these factors and their contributions to AD pathogenesis.This research topic aims to investigate and elucidate the cellular and molecular pathologies of Alzheimer’s Disease, with a particular emphasis on uncovering novel mechanistic links between its diverse etiological factors or molecular pathologies. By exploring both innovative and classical mechanisms, the goal is to bridge existing knowledge gaps in AD pathogenesis and identify new potential therapeutic targets. For instance, one of the key questions includes the role of transglutaminase in tau protein cross-linking, the selective nature of this process, and its broader implications for neuroaxonal transport and neuronal death. Additionally, this research will critically evaluate current therapeutic strategies and propose alternative approaches that may offer greater promise in treating AD.To gain deeper insights into the cellular and molecular pathologies of Alzheimer’s Disease, we invite articles addressing, but not limited to, the following themes:Amyloid betaTau and other cytoskeletal protein abnormalitiesInflammationMetal ion deposition in the AD brain, particularly ironAbnormal calcium ion signalingMolecular and ultrastructural deficits in mitochondriaNovel blood- or cerebrospinal fluid-based biomarkers of AD and their underlying mechanisms in disease pathogenesisWe welcome submissions in various formats, including Mini-Reviews, Brief Research Reports, and Perspectives, to foster a comprehensive understanding of these complex interactions.
Alzheimer’s Disease (AD) is a complex neurodegenerative disorder and the leading cause of dementia worldwide. Despite extensive research, the pathophysiology of AD remains incompletely understood, with multiple hypotheses proposed over the years. These include the amyloid beta (Aβ) and tau protein aggregation theories, inflammation, oxidative stress, metal ion deposition, genetic mutations, calcium signaling abnormalities, and mitochondrial dysfunction. While the Aβ plaque and tauopathy hypotheses have dominated the field, the repeated failure of drug trials targeting these pathways has raised doubts about their validity as therapeutic targets. This underscores the urgent need for a deeper understanding of the disease's multifactorial nature and the interactions between its various etiological factors. Recent studies have begun to explore these intricate interconnections, but significant gaps remain, particularly in elucidating the mechanistic links between these factors and their contributions to AD pathogenesis.This research topic aims to investigate and elucidate the cellular and molecular pathologies of Alzheimer’s Disease, with a particular emphasis on uncovering novel mechanistic links between its diverse etiological factors or molecular pathologies. By exploring both innovative and classical mechanisms, the goal is to bridge existing knowledge gaps in AD pathogenesis and identify new potential therapeutic targets. For instance, one of the key questions includes the role of transglutaminase in tau protein cross-linking, the selective nature of this process, and its broader implications for neuroaxonal transport and neuronal death. Additionally, this research will critically evaluate current therapeutic strategies and propose alternative approaches that may offer greater promise in treating AD.To gain deeper insights into the cellular and molecular pathologies of Alzheimer’s Disease, we invite articles addressing, but not limited to, the following themes:Amyloid betaTau and other cytoskeletal protein abnormalitiesInflammationMetal ion deposition in the AD brain, particularly ironAbnormal calcium ion signalingMolecular and ultrastructural deficits in mitochondriaNovel blood- or cerebrospinal fluid-based biomarkers of AD and their underlying mechanisms in disease pathogenesisWe welcome submissions in various formats, including Mini-Reviews, Brief Research Reports, and Perspectives, to foster a comprehensive understanding of these complex interactions.