Alzheimer’s Disease: Are We Getting Closer to Making a Vaccine against It?

Key Takeaways:

Researchers focus on soluble β-amyloid (β1-14) with a unique hairpin structure, aiming to prevent plaque formation rather than clearing existing ones.
The TAP01 antibody binds to β1-14’s hairpin, triggering an immune response that reduces plaques, preserves glucose metabolism, and protects neurons in mice.
Both the cyclic β1-14 protein and a humanized TAP01 antibody emerge as promising vaccine candidates for Alzheimer’s prevention.
Treated mice, showed 60% fewer plaques, improved brain function, and reduced memory loss compared to controls.
Unlike past failed therapies, targeting aggregated plaques, this approach intercepts amyloid early, potentially halting disease progression.

They are not the first scientists to propose the concept of a vaccine against Alzheimer’s disease. A collaboration between the UK and German scientists aims to create immunity to Alzheimer’s disease by injecting a free form of the amyloid protein responsible for senile plaques. Promising results have just been published in the journal Molecular Psychiatry.

Alzheimer’s disease

For years, scientists looked into the possibility of developing a preventive treatment for Alzheimer’s disease. Various strategies have been tested including targeting both tau and β-amyloid proteins at the same time and enhancing the brain’s immune response. While these approaches have shown promise in early research, they have yet to result in major breakthroughs in Alzheimer’s treatment.

In a study published in Molecular Psychiatry a team of British and German researchers introduced a potential vaccine candidate for Alzheimer’s disease. Trials in mice with the disease showed promising results reducing amyloid plaques and preventing neuronal loss. Instead of targeting already-formed senile plaques, the researchers focused on the soluble forms of the proteins that contribute to their formation—specifically, the untruncated forms of the β-amyloid protein β1-14.

New candidates for a vaccine against Alzheimer’s

At the end of it is a particular hairpin structure, which is the target of an antibody discovered before these experiments. Using crystallography the researchers found that the antibody TAP01 binds to this hairpin protein.

The researchers wanted to find out whether the protein’s hairpin structure was able to elicit a protective immune response against various parameters of Alzheimer’s disease and compared its activity with that of the TAP01 antibody. Mice treated with the cyclic form of β1-14 had fewer senile plaques, but also an active glucose metabolism, a sign of good brain function, and much less neuronal and memory loss.

The researchers believe that β1-14 and the humanized form of TAP01 (which is a mouse antibody) are two interesting candidates for the development of a possible vaccine against Alzheimer’s disease.

FAQs:

How does this Alzheimer’s vaccine work?
It targets soluble β-amyloid’s hairpin structure, prompting antibodies like TAP01 to neutralize the protein before it forms toxic plaques.

Why focus on β1-14 instead of existing plaques?
Early intervention may prevent irreversible neuronal damage. Soluble amyloid is more toxic than plaques, driving cognitive decline earlier.

What’s unique about TAP01?
TAP01 specifically binds to β1-14’s hairpin, a structure absent in healthy, amyloid proteins, minimizing off-target effects.

When could human trials begin?
Preclinical success in mice is a first step. Human trials are likely 3–5 years away, pending safety and efficacy validation.

Could this vaccine reverse Alzheimer’s?
No—it’s preventive. It aims to stop plaque formation in at-risk individuals, not reverse existing damage.

References

Bakrania, P., Hall, G., Bouter, Y. et al. Discovery of a novel pseudo β-hairpin structure of N-truncated amyloid-β for use as a vaccine against Alzheimer’s disease. Mol Psychiatry 27, 840–848 (2022). https://doi.org/10.1038/s41380-021-01385-7

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