On World Alzheimer’s Day 2024, Alzheimer’s disease comes into global focus, especially for researchers working on neurodegenerative diseases. This day provides an opportunity to highlight recent advances and explore new approaches in understanding disease mechanisms like those involving Tau Protein, a central player in Alzheimer’s pathology.

One of the key drivers of Alzheimer’s is the Tau protein, known for forming pathological structures in the brains of Alzheimer’s patients. Little is known about the normal function of Tau in the healthy brain. In a study by Université Laval, “Tau Modulates Visual Plasticity in Adult and Old Mice” which used Striatech’s OptoDrum system, Rodriguez et al. provided new insights into Tau’s role in regulating visual plasticity.

Key Findings: Tau Protein as a Regulator of Adaptive Plasticity

The researchers explored how Tau influences adaptive plasticity in the adult visual system—crucial for understanding how neurons adjust to sensory changes. One example of adult plasticity is the effects of monocular deprivation (MD): While one eye is covered, the visual acuity in the other eye becomes better than normal within only a few days. The researchers could test this using the OptoDrum, which measures visual acuity by taking advantage of the optomotor reflex. But how does Tau influence this plasticity?

The influence of Tau on this plasticity can be assessed with genetically altered mice lacking the Tau protein (Tau KO mice). First, the researchers showed that Tau KO mice had an overall normal visual system: No changes to light responses in the retina, structural integrity of the retina, no unusual cell death, correct ganglion cell connection to the brain, same visual acuity as normal mice when tested with the optomotor reflex, in both young and old animals.

Next, they wondered how the lack of Tau influenced plasticity after monocular deprivation. In this context, it is relevant that there are two isoforms of the Tau protein: Tau 3R and Tau 4R, with three or four regions in the protein, respectively, that bind to microtubules, a structural protein inside of neuronal axons. The researchers showed that during development, the expression level of the two isoforms shift: Early during development, the 3R isoform is dominant both in the retina and in the visual cortex. Its weaker binding to microtubules allows easier changes to neuronal structure, promoting adaptability and plasticity. After the critical period at around 4 weeks of age, expression shifts to the 4R isoform. Its stronger binding to microtubules promotes stability.

The hypothesis was that in adulthood, Tau promotes stability and interferes with plasticity, owing to the 4R isoform. Consequently, they expected the plasticity during adult monocular deprivation to be even stronger in Tau KO mice compared to normal mice, and this was indeed what they have observed: The improvement of vision was so strong that old Tau KO mice even reached levels of visual acuity during monocular deprivation that corresponded to the normal vision in young mice.

In summary, these results allow to draw the following conclusions:

• Age-related effects on plasticity: The study demonstrated that Tau influences visual plasticity not only in young adult mice but also in older animals. This highlights the imporatance to study how Tau supports or limits neuronal function during aging.
• Tau regulates adaptive plasticity: Tau is not only implicated in pathological conditions but also involved in regulating neuronal adaptability in the healthy brain.

Relevance for Alzheimer’s Research

This study highlights the potential link between Tau’s normal role in a healthy brain and its dysregulation in neurodegenerative diseases. Tau’s ability to regulate visual plasticity could be key to identifying mechanisms that break down during Alzheimer’s progression. These findings form a foundation for future therapeutic strategies aimed at improving neuronal adaptability.

Conclusion

On World Alzheimer’s Day, we encourage the scientific community to continue advancing research on Tau and its role in brain plasticity. This study exemplifies how basic research can open new perspectives on Alzheimer’s pathology and other neurodegenerative diseases. We at Striatech are proud to contribute to this work with our expertise and innovative neuroscience testing tools.

You can find the paper here on our website.

Feel free to explore our introduction on measuring the optomotor response for more background information.