Tauopathies as clinicopathological entities.

Area of Science:

• Neuroscience
• Neuropathology
• Genetics

Background:

• Tauopathies are neurodegenerative diseases defined by tau protein inclusions in neurons and glia.
• Evidence suggests tau aggregation is a key driver of neurodegeneration.
• Pathogenic MAPT gene mutations cause hereditary tauopathies.

Purpose of the Study:

• To summarize the current understanding of tauopathies, including their pathology, clinical presentation, and diagnostic challenges.
• To highlight the importance of cell-to-cell tau transmission in disease progression.
• To emphasize the need for improved ante mortem diagnostic methods for tauopathies.

Main Methods:

• Review of animal and cell model studies on tau transmission.
• Analysis of human autopsy data on tau aggregation staging.
• Examination of clinical phenotypes and diagnostic limitations.

Main Results:

• Abnormally modified tau can spread between neurons, potentially recapitulating human disease.
• Human autopsy studies suggest sequential tau aggregation patterns.
• Clinical diagnosis of tauopathies is challenging, often confused with other neurodegenerative diseases.

Conclusions:

• Tau aggregation and cell-to-cell spread are central to tauopathy pathogenesis.
• Current diagnostic criteria lack specificity, necessitating improved ante mortem diagnostic tools.
• Developing therapies to prevent tau pathology spread is crucial for treating tauopathies.