Spotting tau tangles in the brain (Image: Neuron, Maruyama et al)

The two major brain abnormalities that underlie Alzheimer’s disease can now be viewed simultaneously in brain scans while people are still alive, providing new insight into how the disease develops and whether drugs are working.

The breakthrough comes from the development of a harmless tracer chemical that is injected into the bloodstream and accumulates exclusively in “tau tangles” – one type of abnormality that occurs in the brains of people with Alzheimer’s and other kinds of dementia. Fluorescent light emitted from the chemical is picked up using positron emission tomography (PET), showing exactly where the tangles are. The tracer remains in the brain for a few hours before being broken down and expelled from the body.

Similar tracers already exist for beta amyloid plaques, the other major anatomical feature of Alzheimer’s, so the one for tau tangles completes the picture. “This is a big step forward,” says John Hardy, an Alzheimer’s researcher at University College London.


“This is of critical significance, as tau lesions are known to be more intimately associated with neuronal loss than plaques,” says Makoto Higuchi of the National Institute of Radiological Sciences in Chiba, Japan, and head of the team who developed the new tracer.

The tracer could help researchers unravel exactly how Alzheimer’s develops, and enable earlier diagnosis and monitoring of treatments.

Higuchi says that preliminary brain scans using the new tracer in three people with Alzheimer’s and three without, already give new clues about how the disease unfolds. They show that tau tangles accumulate first in the hippocampus – the brain’s memory centre – at a time when the plaques are already widespread.

Previous research has shown that the tangles rapidly kill neurons and trigger behavioural changes. Higuchi says his images suggest that the plaques are themselves harmless, but help to advance disease by spreading the tau tangles from the hippocampus to other brain regions.

Likewise, the extent to which tangles had spread correlated with the severity of disease, and so could serve as a measure of how far the disease has progressed, says Higuchi.

Tracers that reveal amyloid plaques in PET scans arrived in 2005. “They showed that plaques develop much earlier than we thought, sometimes 10 to 15 years before there are symptoms,” says Nick Fox, also at UCL.

“We’ve been able to see one major part of the disease so far, so it will be really helpful to be able to see the other,” says Fox. “The first use could be as a research tool to work out the series of events that lead to disease,” he says. “The pharmaceutical industry will be interested too, to see whether their drugs work.”

Following the repeated failure of drugs targeted at amyloid plaques in people with advanced disease, companies are now trialing drugs for people at a much earlier stage of the disease.

“One reason drugs may not have worked is because they’re too little, too late,” says Fox.

Higuchi is confident that the new tracer, in conjunction with the one for plaques, will help identify those people best suited to early trials, as well as showing through regular brain scans whether they benefit from drugs.

Hardy adds that the tracer will also be useful in research and diagnosis of other dementias that also involve tau tangles, such as supranuclear palsy.

Journal reference: Neuron, DOI: 10.1016/j.neuron.2013.07.037