Tauopathies in Neurodegenerative Disease Pathology

Tauopathies constitute a heterogeneous group of neurodegenerative disorders characterised by the pathological aggregation of tau protein, a microtubule‐associated protein critical for neuronal cytoskeletal stability. Under physiological conditions tau binds to and stabilises microtubules, but aberrant phosphorylation, truncation or conformational changes promote its misfolding and assembly into insoluble inclusions. These inclusions adopt distinct morphologies—neurofibrillary tangles in neurons, astrocytic plaques or tufted astrocytes in astrocytes, and coiled bodies in oligodendrocytes—and their distribution underpins the clinical and pathological features of diseases such as Alzheimer’s disease, progressive supranuclear palsy, corticobasal degeneration and frontotemporal dementia. Tau pathology propagates via a prion‐like mechanism, spreading through connected networks and involving both neuronal and glial compartments. The extent and pattern of tau deposition correlate with cognitive decline, motor deficits and regional vulnerability. Advances in molecular neuropathology have revealed that tau aggregation interacts with comorbid proteinopathies, neuroinflammation and vascular factors, emphasising the need for integrated diagnostic and therapeutic strategies. Biomarker development, including tau PET imaging and fluid assays, has improved in vivo detection, while emerging therapies target tau phosphorylation, aggregation, seeding and clearance pathways. A better understanding of cell‐specific tau dynamics and glial contributions is pivotal to arresting disease progression and restoring network integrity.

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Tauopathies in Neurodegenerative Disease Pathology publication trend

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Technical terms

Tau protein: A stabiliser of neuronal microtubules that becomes pathological when hyperphosphorylated or misfolded.

Tauopathy: A neurodegenerative disease characterised by abnormal tau aggregation in neurons and/or glia.

Neurofibrillary tangle (NFT): Intracellular filamentous aggregates of hyperphosphorylated tau within neurons.

Astrocyte: A glial cell type involved in synaptic support, metabolic regulation and blood–brain barrier maintenance.

Four-repeat tau (4R tau): An isoform of tau containing four microtubule-binding repeats, often enriched in certain tauopathies.

MAPT gene: The gene encoding the tau protein, subject to alternative splicing that generates tau isoforms.

References

1. Argyrophilic grain disease is common in older adults and may be a risk factor for suicide: a study of Japanese forensic autopsy cases. Translational Neurodegeneration (2023).
2. Cell-specific MAPT gene expression is preserved in neuronal and glial tau cytopathologies in progressive supranuclear palsy. Acta Neuropathologica (2023).
3. Astrocytic 4R tau expression drives astrocyte reactivity and dysfunction. JCI Insight (2022).