Follow the tau: This brain protein presents a possible path to earlier Alzheimer’s diagnosis

PROVIDENCE, R.I. [Brown University] - Alzheimer's disease is commonly known for its symptoms - memory loss, cognitive impairment, difficulty with daily tasks - but can only be definitively diagnosed by a look at the brain. A scan must show the abnormal buildup of two distinct brain proteins, beta-amyloid and tau, and it's the dual presence of both that distinguishes the disease from other forms of dementia.

Hwamee Oh, an associate professor of psychiatry and human behavior and of cognitive and psychological sciences at Brown University, is researching different positron emission tomography (PET) imaging methods of detecting Alzheimer's disease as part of the HEAD study, a long-term project involving nine sites in the United States, Canada and Spain. Oh is the principal investigator of the Providence site, which has drawn participants from throughout New England.

In a new study published in the Lancet, HEAD researchers compared the effectiveness of two chemical detectors, called tau tracers, that detect tau in the brain. They found that an experimental tau tracer outperformed a clinically approved tau tracer - a discovery, Oh said, that could pave the way for earlier detection of Alzheimer's disease. In this interview, Oh explains why better detection of Alzheimer's disease is a critical piece of the larger scientific push toward prevention and treatment, and for a patient's trajectory.

Q: How has the detection of Alzheimer's disease evolved over time?

Alzheimer's disease is characterized by the accumulation of beta-amyloid plaques and tau neurofibrillary tangles in the brain. Those pathological features were first described in 1906 by Alois Alzheimer, but it wasn't until 2004 that we developed a PET imaging method to identify beta-amyloid plaques in living people. For tau, it was 2012.

Q: What are some challenges in diagnosing Alzheimer's?

Currently, behavioral changes are an important part of diagnosing Alzheimer's disease. But these symptoms can derive from many different causes. That's why neuroimaging plays a key role. If someone presents symptoms of mild cognitive impairment, a clinician would recommend a PET scan to definitively determine their type of dementia. And that, in turn, would determine different treatment strategies for that person.

Because PET imaging is costly, one of the ongoing efforts in our lab - in collaboration with other Brown researchers and affiliated hospitals - is to develop more sophisticated behavioral markers using cognitive and computational approaches. Hopefully, these developments will facilitate earlier detection of disease-related brain changes.

Q: Your research has focused on the detection of tau. What's so significant about these proteins in the development of Alzheimer's disease?

We don't actually know how tau tangles lead to the clinical symptoms of Alzheimer's disease. But we do know that tau is closely related to cognitive decline. If you see an abnormal presentation of tau - such as tangles or other buildup - in a part of the brain, you will probably see neuron loss in that same region later on. In fact, tau is linked to other neurodegenerative diseases, such as frontotemporal dementia. For Alzheimer's, what's interesting is that while beta-amyloid plaques rarely appear in the human brain before age 45, abnormal tau can be detected much younger - even in the brains of people in their teens and 20s.