Vaccine Reduces Tau Tangle Formation, Improves Cognitive Functioning in Alzheimer’s Mouse Model

A vaccine produced using virus-like particles was able to improve cognitive functioning and reduce the accumulation of tau protein aggregates — a hallmark of Alzheimer’s disease — in a mouse model of the disease, a study shows.

The study, “Qß Virus-like particle-based vaccine induces robust immunity and protects against tauopathy,” was published in the journal NPJ Vaccines.

The characteristic features of Alzheimer’s disease, such as disrupted communication between nerve cells, are thought to be partly caused by the presence of abnormal protein aggregates — amyloid plaques and tau tangles — in the brain.

Previous research has shown that antibodies targeting the hyperphosphorylated form of the tau protein — when the protein becomes heavily tagged with phosphor-molecules promoting its aggregation into tangles — are relatively safe and effective at reducing tau accumulation. Some of these therapies are being tested in clinical trials, such as Genentech’s RO7105705 or AbbVie’s ABBV-8E12. However, there are disadvantages to these kinds of therapies, including high cost and the need for repeated administrations.

Researchers at the University of New Mexico now have developed a vaccine that can target tau and may help overcome some of these limitations.

The vaccine uses virus-like particles derived from viruses whose genome (genetic information) has been removed, but the outer protein shell of the virus remains. The removal of the virus genome prevents its reproduction. However, keeping the outer protein shell is enough to trigger an immune response from the body. In this case, researchers attached a section of the tau protein to the surface of the virus-like particles, triggering an immune response against the toxic form of this protein and resulting in the elimination of tau tangles.

To assess the effects of the vaccine, researchers vaccinated mice that had tau protein aggregates in the brain, which resulted in the production of antibodies that efficiently removed tau tangles from the brain. This response lasted several months.

Using magnetic resonance imaging (MRI) to visualize what was occuring in the brain, the team observed that mice treated with the vaccine had less brain shrinkage, suggesting that the vaccine may stop neuronal cell death.

Furthermore, vaccinated mice had less tau tangles present in specific regions of the brain that are important for learning and memory and are affected in Alzheimer’s disease, namely the cortex and hippocampus.

The vaccine did not show a pro-inflammatory response and instead reduced the activation of microglia — immune cells of the central nervous system — and the number of circulating T-cells (a type of immune cells) in the brain.

Importantly, vaccinated mice performed better in maze-like tests, which assess cognitive functioning.

This vaccine may be able to stop the formation of tau tangles and cognitive decline that occurs in Alzheimer’s disease patients.

Researchers now hope to obtain funding from a federal Small Business Innovation Research grant to further test this vaccine, including potential clinical trials in Alzheimer’s patients.

“We’re excited by these findings, because they seem to suggest that we can use the body’s own immune system to make antibodies against these tangles, and that these antibodies actually bind and clear these tau tangles,” Nicole Maphis, a researcher at the University of New Mexico and the study’s first author said in a press release.

“These results confirm that targeting tau tangles using a vaccine intervention could rescue memory impairments and prevent neurons from dying,” Maphis added.