Differences Between Human and Murine Tau at the N-terminal End

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Transgenic mice overexpressing human tau are key models for studying human tauopathies, including Alzheimer's disease (AD).
• While mouse and human tau proteins share high amino acid identity (89%), significant differences exist in isoform expression and N-terminal sequences.
• Specifically, adult mice lack Tau 3R isoforms present in humans, and a unique N-terminal peptide (residues 17-28) is found in human tau but not mouse tau.

Purpose of the Study:

• To review existing data on the differences between human and mouse tau proteins, particularly concerning their N-terminal sequences.
• To explore the functional implications of these differences on protein interactions and secretion patterns.
• To highlight the importance of these distinctions for the accurate modeling of human tauopathies in mice.

Main Methods:

• Review of published literature on human and mouse tau protein characteristics.
• Comparative analysis of tau protein sequences and isoform expression patterns.
• Examination of studies investigating tau protein interactions and secretion.

Main Results:

• Human tau exists as 3R and 4R isoforms in the adult brain, whereas adult mice only express 4R isoforms.
• A distinct N-terminal peptide (residues 17-28) is present in human tau but absent in mouse tau.
• The N-terminal sequence differences suggest variations in interactions with endogenous proteins and distinct secretion patterns between human and mouse tau.

Conclusions:

• The differences in tau isoform expression and N-terminal sequences between humans and mice have significant implications for their biological functions.
• These species-specific variations may lead to differential interactions with cellular components and distinct secretion mechanisms.
• Understanding these molecular distinctions is critical for interpreting results from mouse models used to study human tauopathies and Alzheimer's disease.