Tau and neurodegeneration

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Tau protein, identified in 1975, was linked to Alzheimer's disease in 1985.
• Hyperphosphorylated tau forms filamentous inclusions in neurodegenerative diseases, including frontotemporal dementia caused by MAPT gene mutations.
• Most tauopathies are sporadic, but tau filament assembly can drive neurodegeneration and dementia.

Purpose of the Study:

• To summarize the historical understanding and recent advancements in tau research.
• To highlight the role of tau pathology in neurodegenerative diseases.
• To explain the prion-like spread of tau pathology and its implications for disease classification.

Main Methods:

• Historical literature review.
• Analysis of genetic studies identifying MAPT mutations.
• Review of experimental systems demonstrating tau spread.
• Examination of high-resolution structural studies on human brain tauopathies.

Main Results:

• Tau pathology is central to Alzheimer's disease and other tauopathies.
• Mutations in the MAPT gene cause inherited frontotemporal dementia with tau inclusions.
• Filamentous tau assemblies can propagate in a prion-like manner across brain regions.
• Structure-based classification of tauopathies has advanced understanding of filament formation.

Conclusions:

• Aberrant tau assembly is sufficient to cause neurodegeneration and dementia.
• Understanding tau filament formation and spread is crucial for classifying and potentially treating tauopathies.
• Recent structural studies offer new insights into the mechanisms of tauopathies.