Evidence from human neuropathology and recent neuroimaging studies indicates that the burden of tau neurofibrillary tangles progressively spreads along anatomical connections over several years, culminating in neurodegeneration and cognitive decline in Alzheimer’s disease (AD). Amyloid beta accumulation appears to enhance the spread and pathogenicity of tau. However, in addition to amyloid plaques, Alzheimer’s disease frequently occurs with co-pathologies including alpha-synuclein containing Lewy bodies, TDP-43 inclusions, or vascular changes.
These co-pathologies may be either coincident disease processes that occur with aging or—as suggested by human and animal studies—they may alter the formation of tau aggregates or rate of spread. In following, key questions for the field include whether these pathological changes interact with tau though direct “cross-seeding” events, convergent cell-autonomous mechanisms, or indirect interactions involving inflammatory mediators.
Advances in this area of research are made possible by increasingly widespread use of new techniques. For example, improvements in PET tracers and sensitive MRI methods allow investigation of tau accumulation in relation changes in other protein aggregates, gliosis, and vascular function. Innovative animal and cell culture models can be used to test interactions with tau through co-expression or injection of pathological aggregates into brain. Multiphoton and cell-tracking systems make it possible to visualize tangle formation and measure tau kinetics in situ. Single cell-level transcriptomic data can be used to aid in determining if these are cell autonomous or non-cell autonomous processes and identify new mechanistic pathways that influence tau spread.
Understanding the role of these co-pathologies and other modifiers, could lead to new therapeutic approaches for slowing detrimental tau accumulation and could help explain the impact of amyloid beta modifying therapies on tau biomarkers in recent clinical trials.
This Research Topic will welcome Original work, Methods, Perspectives and Reviews of neuropathological, neuroimaging, animal model and in vitro studies that:
• Improve our understanding of the spatial and temporal relationships between tau and co-occurring pathologies
• Expand our knowledge of factors that influence tau spread in the brain or in model systems
• Investigate mechanistic pathways that contribute to altered tau pathology in various contexts (e.g. with alpha-synuclein aggregates, aging, gliosis, sex differences).
• Use in vitro and biochemical methods to explore tau-interacting proteins and co-factors impacting aggregation
Evidence from human neuropathology and recent neuroimaging studies indicates that the burden of tau neurofibrillary tangles progressively spreads along anatomical connections over several years, culminating in neurodegeneration and cognitive decline in Alzheimer’s disease (AD). Amyloid beta accumulation appears to enhance the spread and pathogenicity of tau. However, in addition to amyloid plaques, Alzheimer’s disease frequently occurs with co-pathologies including alpha-synuclein containing Lewy bodies, TDP-43 inclusions, or vascular changes.
These co-pathologies may be either coincident disease processes that occur with aging or—as suggested by human and animal studies—they may alter the formation of tau aggregates or rate of spread. In following, key questions for the field include whether these pathological changes interact with tau though direct “cross-seeding” events, convergent cell-autonomous mechanisms, or indirect interactions involving inflammatory mediators.
Advances in this area of research are made possible by increasingly widespread use of new techniques. For example, improvements in PET tracers and sensitive MRI methods allow investigation of tau accumulation in relation changes in other protein aggregates, gliosis, and vascular function. Innovative animal and cell culture models can be used to test interactions with tau through co-expression or injection of pathological aggregates into brain. Multiphoton and cell-tracking systems make it possible to visualize tangle formation and measure tau kinetics in situ. Single cell-level transcriptomic data can be used to aid in determining if these are cell autonomous or non-cell autonomous processes and identify new mechanistic pathways that influence tau spread.
Understanding the role of these co-pathologies and other modifiers, could lead to new therapeutic approaches for slowing detrimental tau accumulation and could help explain the impact of amyloid beta modifying therapies on tau biomarkers in recent clinical trials.
This Research Topic will welcome Original work, Methods, Perspectives and Reviews of neuropathological, neuroimaging, animal model and in vitro studies that:
• Improve our understanding of the spatial and temporal relationships between tau and co-occurring pathologies
• Expand our knowledge of factors that influence tau spread in the brain or in model systems
• Investigate mechanistic pathways that contribute to altered tau pathology in various contexts (e.g. with alpha-synuclein aggregates, aging, gliosis, sex differences).
• Use in vitro and biochemical methods to explore tau-interacting proteins and co-factors impacting aggregation