Queensland Brain Institute (QBI) researchers have generated a promising Tau antibody as a potential immunotherapy treatment aimed at targeting harmful protein aggregates in Alzheimer’s disease.
Alzheimer's disease, the most common type of dementia, has two hallmark signs that appear in the brain: amyloid plaques and Tau tangles. The toxic Tau protein causes various proteins in the brain to become dysregulated, with some increasing and others decreasing in abundance.
Now, researchers have generated and characterised a new antibody that can restore the protein balance.
Dr Esteban Cruz Gonzalez and Professor Jürgen Götz from the Clem Jones Centre for Ageing Dementia Research (CJCADR) said their findings reveal a key aspect in achieving a successful treatment outcome, highlighting its potential to change the course of disease significantly.
“We were surprised to find that this new antibody can not only target Tau but can also restore the protein imbalance caused by the disease,” said Dr Cruz.
“This finding suggests that the antibody’s potential efficacy extends beyond just targeting Tau; it also restores the healthy levels of interaction, reestablishing equilibrium in the brain.”
In a study published in Brain, the researchers generated and tested a novel Tau antibody, RNJ1, in mice with Alzheimer’s-like disease. This new antibody was benchmarked against the clinically tested Tau antibody tilavonemab and improvements in motor function and Tau build-up were carefully tracked.
“Both antibodies demonstrated a reduction in Tau pathology following 14 weekly treatments, but the RNJ1 antibody was superior in restoring behavioural functions and inducing widespread changes in many other proteins, suggesting that the treatment helped rescue various cellular processes affected by Tau,” said Dr Cruz.
A key point of the study was a thorough analysis of over 6,000 proteins and their activity levels in normal mice, mice with Alzheimer’s-like disease, and those treated with the antibodies.
This detailed examination allowed the researchers to identify many cellular processes affected by the Tau protein. They found that antibody treatment helped restore the balance of proteins in the brain, and this restoration was linked to the effectiveness of the treatment.
Dr Cruz noted that while there are currently three antibodies recently approved for Alzheimer's disease that target amyloid-beta plaques, several Tau-targeting antibodies are still in clinical development and have not yet been approved for clinical use.
“The development of immunotherapies for amyloid-beta is the lower-hanging fruit because it’s in the extracellular space, which makes it a much easier target to reach,” said Dr Cruz.
“With Tau, an antibody must first cross the blood-brain barrier and then get into the neuron.
“At the moment, we’re using high doses of antibody but only a small fraction of it crosses the blood-brain barrier and, from that small fraction, only another very small percentage goes into the neurons and reaches their target.
“The exciting part of this research is that this outcome not only validates the therapy's potential effectiveness but also demonstrates the antibody's ability to restore broader brain function.”
Professor Götz said using low-intensity scanning ultrasound in conjunction with this new antibody may further improve therapeutic outcomes, highlighting the potential to integrate pharmacological and nonpharmacological approaches for Alzheimer’s disease treatment.
“The team will continue to work on this research to further increase the efficacy of the antibody,” he said.
