Tau and saitohin gene expression pattern in progressive supranuclear palsy

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Progressive supranuclear palsy (PSP) is a neurodegenerative disease.
• Tau mRNA splicing deregulation, affecting microtubule-binding repeat isoforms (4R and 3R), is implicated in PSP.
• Saitohin (STH), a nested gene in tau intron 9, may also play a role in PSP pathogenesis.

Purpose of the Study:

• To investigate tau mRNA isoform expression and Saitohin (STH) mRNA levels in the brains of PSP patients.
• To compare these levels with those in healthy controls and Alzheimer's disease (AD) patients.
• To explore the relationship between tau mRNA splicing, specifically the 4R/3R ratio, and STH expression in PSP.

Main Methods:

• Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure mRNA levels.
• Analysis was performed on brain tissue from the frontal cortex and globus pallidus.
• Samples were obtained from PSP patients, healthy controls, and Alzheimer's disease (AD) patients.

Main Results:

• The 4R/3R tau mRNA ratio was significantly elevated in the globus pallidus of PSP patients compared to controls.
• 0N tau mRNA isoform levels were higher in both frontal cortex and globus pallidus of AD patients, and borderline higher in PSP globus pallidus.
• A significant positive correlation was observed between the 4R/3R tau mRNA ratio and STH expression across all sample groups, stronger in the globus pallidus.

Conclusions:

• Aberrant alternative splicing of the tau gene contributes to the molecular mechanisms underlying PSP.
• Increased 4R/3R tau mRNA ratio and potential overexpression of 0N tau isoforms are associated with PSP pathogenesis.
• The correlation between tau splicing and STH expression suggests a potential interplay in neurodegenerative processes.