Investigators Develop Potential Vaccine, Treatment for Alzheimer Disease Using Novel Drug Target

Investigators have developed an antibody-based treatment for Alzheimer disease, as well as a protein-based vaccine, according to a study published in Molecular Psychiatry. These 2 treatments were shown to reduce symptoms of Alzheimer disease in mouse models.

“In clinical trials, none of the potential treatments which dissolve amyloid plaques in the brain have shown much success in terms of reducing Alzheimer's symptoms,” said Thomas Bayer, MD, in a press release. “Some have even shown negative side effects. So, we decided on a different approach. We identified an antibody in mice that would neutralize the truncated forms of soluble amyloid beta but would not bind either to normal forms of the protein or to the plaques.”

Amyloid beta protein naturally exists as highly flexible, string-like molecules in solution, which can join together to form fibers and plaques. In Alzheimer disease, a high proportion of these string-like molecules become shortened or 'truncated,' which investigators suspect could be key to the development and progression of the disease. Both the antibody and the vaccine target this soluble form of the protein, which is thought to be highly toxic. When observing how and where the adapted antibody binds to the truncated form of amyloid beta, they found that the amyloid beta protein was folded back on itself in a hairpin-shaped structure.

“This structure had never been seen before in amyloid beta,” said Mark Carr, PhD, in the release. “However, discovering such a definite structure allowed the team to engineer this region of the protein to stabilize the hairpin shape and bind to the antibody in the same way. Our idea was that this engineered form of amyloid beta could potentially be used as a vaccine, to trigger someone's immune system to make TAP01_04 type antibodies.”

The investigators tested both the antibody and the engineered amyloid beta vaccine TAPAS in 2 different mouse models of Alzheimer disease. According to the results, both the antibody and the vaccine helped to restore neuron function, increase the brain’s glucose metabolism, and restore memory loss. Additionally, although neither treatment targeted amyloid beta plaques directly, both treatments reduced amyloid beta plaque formation.

“The TAP01_04 humanized antibody and the TAPAS vaccine are very different to previous antibodies or vaccines for Alzheimer disease that have been tested in clinical trials, because they target a different form of the protein,” said Preeti Bakrania, PhD, in the press release. “This makes them really promising as a potential treatment for the disease either as a therapeutic antibody or a vaccine. The results so far are very exciting and testament to the scientific expertise of the team. If the treatment does prove successful, it could transform the lives of many patients.”

REFERENCE

New approach provides potential vaccine and treatment for Alzheimer’s [news release]. Science Daily; November 14, 2021. Accessed November 24, 2021. https://www.sciencedaily.com/releases/2021/11/211114201756.htm