Next Phase in Alzheimer's Treatment: Clinical Trials for Tau-Targeting Vaccine

Researchers at the University of New Mexico are progressing toward human clinical trials for an experimental vaccine designed to prevent the accumulation of abnormal tau protein in the brain, a hallmark of Alzheimer's disease. Published in the journal Alzheimer's & Dementia, the study reports that this vaccine has successfully stimulated a strong immune response in mice and non-human primates, bringing it closer to potential human application.

Led by Professor Kiran Bhaskar, the research builds on earlier findings where the vaccine prompted the production of antibodies targeting a specific form of the tau protein, pT181, associated with Alzheimer’s pathology. In animal models, including macaques with immune systems similar to humans, the vaccine reduced tau tangles and improved cognitive function. These promising results have encouraged the team to seek funding for a Phase 1 human trial.

Tau is a naturally occurring protein that stabilizes neurons, but in Alzheimer’s and other neurodegenerative diseases, it undergoes abnormal phosphorylation, causing it to form toxic tangles that disrupt neural function. Current treatments targeting amyloid beta—the other major protein linked to Alzheimer’s—offer limited benefits, prompting scientists to explore tau as a more effective target.

The vaccine utilizes a virus-like particle (VLP) platform, developed by collaborators Bryce Chackerian and David Peabody, that effectively introduces pieces of the tau protein to the immune system without causing disease. This approach has shown to produce durable immune responses with a simple vaccination schedule, without the need for additional adjuvants, and has been demonstrated to be safe in previous trials.

In further validation, blood serum from vaccinated monkeys was tested against human blood samples and brain tissue, confirming the vaccine’s ability to generate antibodies that recognize the human tau protein. Nicole Maphis, the lead author, emphasized the importance of validation in animals with immune systems comparable to humans, which enhances confidence in future clinical trials.

The research team is currently seeking funding from venture capitalists and the Alzheimer’s Association to move forward with Phase 1 testing. This innovative approach could provide a new avenue for Alzheimer’s treatment focusing on tau, potentially slowing or preventing disease progression.

For more details, please refer to the publication: Nicole M. Maphis et al, 'Targeting of phosphorylated tau at threonine 181 by a Qβ virus-like particle vaccine is safe, highly immunogenic, and reduces disease severity in mice and rhesus macaques,' Alzheimer's & Dementia (2025).