Researchers in Japan have developed a new brain scan to detect the build-up of a protein called tau, which is involved in Alzheimer’s and frontotemporal dementia. The study is published on Wednesday 18 September in the journal Neuron.
Tau is one of two proteins that accumulate inside the brain as Alzheimer’s disease develops. The other, amyloid, can already be ‘seen’ in the living brain using sophisticated brain scans, but the presence of amyloid is not enough to confirm that a person has Alzheimer’s, meaning these existing scans have limited use for detecting the disease. Tau is also involved in other diseases including frontotemporal dementia (FTD) – a rare form of dementia that can cause personality and behaviour changes as well as problems with language and thinking. The team at the National Institute of Radiological Sciences in Chiba set out to develop a new scan to detect tau in the brain, in the hope of improving the ability to detect these diseases.
Existing scans for detecting amyloid work by injecting a compound that binds to the protein inside the brain before the person undergoes a PET brain imaging scan. Because this compound includes a fluorescent ‘tag’ that can be picked up by the scan, it’s then possible to see how much amyloid is present, and where it is located in the brain.
To detect tau in a similar way, the researchers began by developing a new class of fluorescent compounds, called PBBs. When they added them to brain samples from people who died with Alzheimer’s or FTD, they found that these were able to bind to tau. The team then tested the compound in mice bred to develop features of Alzheimer’s, and again found that it bound to tau, with the protein showing up on a PET scan.
They then took forward one of these compounds, called [11C]PBB3, for further investigation in three volunteers with Alzheimer’s disease and three healthy people. After injection with the compound, PET scans showed tau build-up in certain areas of the brain in all three Alzheimer’s patients, while only one of the healthy participants showed any tau present in the brain. Further investigation showed this participant had worse scores than the other healthy volunteers on an MMSE – a cognitive test commonly used to help diagnose Alzheimer’s disease.
Dr Eric Karran, Director of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, said:
“This promising early study highlights a potential new method for detecting tau – a key player in both Alzheimer’s and frontotemporal dementia – in the living brain. With new drugs in development designed to target tau, scans capable of visualising the protein inside the brain could be important for assessing whether treatments in clinical trials are hitting their target. If this method is shown to be effective, such a scan could also be a useful aid for providing people with an accurate diagnosis, as well as for monitoring disease progression. Larger and more long-term studies are needed to confirm these findings and investigate how well these scans can track the build-up of tau over time.
“For results like these to be translated into a tool that would be suitable for widespread use, investment in research is crucial. The different forms of dementia can be extremely difficult to diagnose accurately using currently available methods, and research to improve these methods is important if we are to help people access the right care and treatments.