Mouse and Human Tau Expression in Different Brain Areas.

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Increased tau protein is a prerequisite for tau aggregation.
• The source of elevated tau—increased gene expression or proteostasis failure—remains unclear.

Purpose of the Study:

• To investigate tau (MAPT) gene promoter expression across various brain regions and ages.
• To differentiate between transcriptional changes and proteostasis failure in tau accumulation.

Main Methods:

• Utilized tau knockout mice with GFP-encoding cDNA integrated into the MAPT gene.
• Measured direct MAPT gene promoter expression via Western blot and immunofluorescence.
• Analyzed MAPT gene expression in human brain samples.

Main Results:

• Consistent MAPT gene expression observed in mouse and human cortex, hippocampus, and cerebellum.
• Minor variations in expression noted between mouse dentate gyrus and CA1 hippocampal areas.
• No significant changes in endogenous tau promoter expression detected during aging in mice (2-18 months).

Conclusions:

• MAPT promoter activity is uniform across major brain regions studied.
• Tau accumulation during aging is more likely attributed to proteostasis failure than transcriptional upregulation.