Abstract
Tauopathies are a diverse group of progressive and fatal neurodegenerative diseases characterized by aberrant tau inclusions in the central nervous system. Tau protein forms pathologic fibrillar aggregates that are typically closely associated with neuronal cell death, leading to varied clinical phenotypes including dementia, movement disorders, and motor neuron disease. In this review, we describe the clinicopathologic features of tauopathies and highlight recent advances in understanding the mechanisms that lead to spread of pathologic aggregates through interconnected neuronal pathways. The cell-to-cell propagation of tauopathy is then linked to posttranslational modifications, tau fibril structural variants, and the breakdown of cellular protein quality control.
🔬 Techniques
🧬 Organisms
✨ Fluorophores
🧪 Sample Preparation
🔬 Cell Lines
🏭 Microscope Brands
💻 Software Details
💾 Data Repositories
🏛️ Research Organizations (ROR)
Affiliated research institutions:
📊 Figures
Figure 1
Pathogenic variants and major splicing variants of tau. Tau is encoded by the MAPT gene on chromosome 17 in humans that contains 16 exons of which exons 1, 4, 5, 7, 9, 11, 12, and 13 are constitutivel...
Figure 2
Posttranslational modifications (PTMs) of disease-relevant tau fibrils. Sarkosyl-insoluble tau fibrils are found in cognitively normal individuals with primary age-related tauopathy (PART) and cogniti...
Figure 3
Immunohistochemistry of various tau inclusions, including examples of a neurofibrillary tangle (NFT), Pick body, tufted astrocyte, pretangle, coiled body, thorn-shaped astrocyte, globular astrocytic i...
Figure 4
Disease-associated tau fibril cryogenic electron microscopy structures. Diseases with a high-resolution fibril structure are listed with pathologic inclusions found and tau isoform present by immunohi...
Figure 5
Schematic of tau aggregate clearance pathways. For the ubiquitin-proteasome system (UPS) and macroautophagy, ubiquitin is added to aggregates via a cascade of ubiquitin-activating enzymes (E1s) and ub...
Figure images are served from the NIH/NLM PubMed Central Open Access Subset or Europe PMC; copyright remains with the publishers and authors.
💬 Discussion
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