Tauopathies: recent insights into old diseases

Area of Science:

• Neuroscience
• Neuropathology
• Genetics

Background:

• Neurofibrillary tangles (NFTs) are intra-neuronal lesions identified via histological silver staining.
• NFTs represent a key feature of neurofibrillary degeneration (NFD), a process involving tau protein.

Observation:

• NFTs are present in over 20 neurodegenerative disorders, indicating NFD's role across diverse etiologies.
• The morphology and biochemistry of tangles, including paired helical filaments (PHFs) in Alzheimer's disease, are disease-specific.
• Tau aggregates exhibit unique biochemical profiles based on tau isoform aggregation and distinct spatio-temporal progression patterns correlating with cognitive decline.

Findings:

• Pathological tau mutations cause familial fronto-temporal diseases with parkinsonism (FTDP-17).
• The concept of tauopathies unifies these observations, defining each by clinical, neuropathological, biochemical, and genetic features.
• Most tauopathies involve specific tau defects (mutations, splicing, phosphorylation, processing, or vulnerability), linking etiology to tau dysfunction.

Implications:

• Most dementing disorders are classified as tauopathies.
• Tauopathy diagnosis and understanding are crucial for managing dementing illnesses.
• Targeting tau dysfunction presents a therapeutic avenue for neurodegenerative diseases.