Australasian Science: Australia's authority on science since 1938

Alzheimer’s Vaccine Slows Development of Tangles

By Stephen Luntz

Vaccine shows promise for Alzheimer's and early-onset dementia.

A vaccine has proven effective against a neural disease in mice that is considered a model for both Alzheimer’s disease and frontal temporal dementia, the second most common form of early onset dementia.

Attempts to stop Alzheimer’s disease have focused on preventing the accumulation of amyloid betaplaques associated with the condition. Instead, A/Prof Lars Ittner of the University of Sydney’s Brain and Mind Research Institute has concentrated on the tau protein, which is present in both conditions and is believed to drive the formation of neurofibrillary tangles.

Ittner says the plaques were considered “more promising from an immunological point of view. It is an extracellular protein, where tau is an intracellular one,” he says. “To affect tau you have to not only pass the blood–brain barrier but also get into cells. However, there are other examples of intracellular proteins that have been targeted for vaccines, and we’re not the only ones to get it to work.” Moreover, the tau protein has the strongest correlation with the progression of both diseases.

Ittner acknowledges that animal models have limitations, particularly in this case where only one gene is involved in the mouse while several are important for humans. Nevertheless, he is buoyed by the results. “The vaccine appears to have a preventative effect – slowing the development of further tangles rather than clearing existing ones – but the exact mechanism involved is not yet understood,” he says.

Mice with the model condition do not get plaques as humans do, but Ittner says that in another model the removal of the tau protein without changing the plaque concentration eliminated the disease’s pathology. “We think tau is downstream of the plaques. Plaques are not a good thing to have, but as long as there is no tau around they are not a huge problem,” he says.

Other vaccines have shown success against the tau protein in mice, but Ittner says these were tested before the mice showed any symptoms, earlier than humans are diagnosed. In this case mice that were already sick became more active and life expectancy returned to normal. “When we look at the brains after they have died, a mouse at the end of treatment looks like a mouse at the point where the treatment was applied.”

Ittner says that collaboration has begun with an American pharmaceutical company to trial passive immunisation, where antibodies are provided continuously as a drug rather than using a triggering injection. He says passive immunisation seems safer in this case, and can also be switched off if necessary, since the tau protein has a role in the body maintaining the structure of neurons. Other roles may also exist but are not well understood.