Tauopathy
Neurodegenerative diseases marked by abnormal tau protein aggregation.
Tauopathies are a broad category of neurodegenerative disorders defined by the abnormal aggregation of tau protein within neurons and glial cells. Hyperphosphorylation of tau leads to its detachment from microtubules and the formation of insoluble neurofibrillary tangles. These diseases are classified as primary tauopathies when tau deposition is the dominant feature, or secondary tauopathies when tau pathology arises from other underlying causes.
Quick Facts
- Psp prevalence
- 5-6.4 per 100,000 people
- Tau isoform length range
- 352 to 441 amino acids
- Number of tau isoforms
- 6
- Psp tau type
- 4R tauopathy
- Pick body tau bands
- 60 and 64 kDa major, 69 kDa minor
Facts from the source article.
Did You Know?
- Tau protein is also called tubulin associated unit or microtubule-associated protein tau (MAPT).
- Tau isoforms arise through alternative splicing of exons 2, 3 and 10 within the MAPT gene.
- The six tau isoforms are differentiated by inclusion or exclusion of 29- or 58-amino-acid inserts in the N-terminus domain.
Biomarkers
Positron emission tomography (PET) can detect elevated tau levels in Alzheimer's disease, offering spatial information on neuropathologic burden, though it is limited by cost, accessibility, and minimal radioactivity exposure. Cerebrospinal fluid (CSF) analysis provides another biomarker avenue; in Alzheimer's disease, elevated CSF tau combined with decreased amyloid-beta levels forms a characteristic signature that can differentiate patients from controls and may help distinguish atypical AD pathology from frontotemporal lobar degeneration with tau pathology.
Pathologic phenotypes of tauopathies
Alzheimer's disease (AD) is a secondary tauopathy featuring both extracellular amyloid-beta plaques and intracellular neurofibrillary tangles of hyperphosphorylated tau. The amyloid cascade hypothesis proposes that amyloid-beta accumulation initiates AD pathogenesis, with tauopathy as a downstream consequence. Frontotemporal dementia (FTD) within the frontotemporal lobar degeneration spectrum shows profound neuronal loss, enlarged neurons, and spherical argyrophilic Pick bodies composed mainly of 3R tau isoforms. Progressive Supranuclear Palsy (PSP) is a rare 4R tauopathy presenting with supranuclear gaze palsy, postural instability, motor abnormalities, and cognitive impairment; it is characterized by tufted astrocytes and abnormal tau in both neurons and glial cells, and is considered a relatively pure tauopathy often selected for anti-tau therapeutic trials.
Other tauopathies
Dozens of disorders involve abnormal tau aggregates in the central nervous system. Examples include primary age-related tauopathy (PART) with neurofibrillary tangles but no amyloid-beta plaques, chronic traumatic encephalopathy (CTE), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), vacuolar tauopathy associated with VCP gene mutation, Lytico-bodig disease, ganglioglioma, meningioangiomatosis, subacute sclerosing panencephalitis, lead encephalopathy, tuberous sclerosis, pantothenate kinase-associated neurodegeneration, and lipofuscinosis.
Tau therapeutics
No specific disease-modifying treatments exist for tauopathies. In Alzheimer's disease, both tau phosphorylation changes and amyloid-beta alterations are thought to begin more than 20 years before symptom onset, complicating treatment development. Symptom relief is available through speech therapy for aphasia, pharmaceuticals for depression and apathy, and physical therapy to extend motor function.
More in Cytoskeletal Defects
Spotted an error? Know more?
Reader corrections go straight into our review queue. Suggest an edit · How this site is sourced