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What are the biological mechanisms by which abnormal tau accumulates and moves in the brain in Alzheimer’s and other brain diseases?
Daniel Chain, Ph.D.
TauC3 Biologics Limited
London, United Kingdom
Background
The brain nerve cell’s nutrient and energy transport system is organized in parallel strands like railroad tracks. These tracks allow nutrients to travel across the cell, delivering key materials to the points of connection with other nerve cells, providing them with energy and keeping them healthy. The tau protein helps keep these tracks straight. However, in Alzheimer’s, frontotemporal dementia and over 20 other brain diseases the shape of tau protein becomes modified or “misfolded” and this could contribute to tau tangles (a hallmark of these diseases) and subsequent nerve cell damage.
Recent studies show that certain variations of tau are released from nerve cells which may act as “seeds”. These “seeds” could lead to the formation, transportation, and clumping of variations of abnormal tau. Studies also show that a particular variation of tau, called tauC3, may be especially important in tau seeding and movement. Recently, researchers have tested an antibody designed to block tauC3. They found that the antibody may be effective at reducing tau accumulation in mouse nerve cells in a laboratory dish.
Research Plan
Dr. Chain and colleagues will further study how tauC3 may be associated with tau seeding and abnormal tau accumulation in mice genetically engineered to develop human tau. To do so, the researchers will administer tau with and without the tauC3 variation to the animals’ brains and evaluate the downstream impact on tau. If these experiments are successful, Dr. Chain and his team will study how two different tauC3 antibodies may prevent the tau seeding and transportation of abnormal tau in the brain regions of these mice.
Impact
The study results could help develop a potential therapeutic antibody which may help prevent the accumulation of abnormal tau in the brain in Alzheimer’s and other abnormal tau-related brain diseases. If successful, the results may identify the biological mechanisms associated with seeding and movement of abnormal tau throughout the brain.
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