Evidence Grows for Role of Tau in Early Prediction, Intervention of Alzheimer’s Disease

For more than a decade, evidence has mounted that misfolded tau proteins in brain cells likely contribute to Alzheimer’s disease, in addition to the presence of amyloid-beta protein. Now, BrightFocus-funded research offers even more evidence of the importance of tau in the prediction and early detection of Alzheimer’s disease which could lead to ways to delay—or even stop—the disease from progressing.

The research was conducted by Alzheimer’s Disease Research-funded grantee Alexa Pichet Binette, PhD, of Lunde University in Malmö, Sweden.

Dr. Binette and her team found that older adults with intact cognition, but with significant amounts of amyloid-beta and tau in their brains, were much more likely to develop cognitive impairment or dementia within a few years.

In contrast, people with no detectable amyloid-beta and tau were not as likely to develop cognitive impairment or dementia. The same was true for people with only amyloid beta in their brains. This finding highlights the critical role of tau in disease progression and shows that the presence of tau can be an early predictor of Alzheimer’s disease onset and potentially treatable with drugs.

Although there is no cure for Alzheimer’s, early detection is extremely important to help delay its progression and for interventions to be successful.

Predictive measures take this a step further to devise even earlier treatment strategies.

In a separate study, Dr. Binette found that one form of tau (soluble phosphorylated-tau) is highly predictive of later accumulation of tau aggregates in the brain and cognitive decline. This was found to be especially true in the early phase of Alzheimer’s. This finding can help identify rapid progressors and provide a way to disrupt this process to delay or prevent further disease progression.

“Overall, tau pathology is playing an increasingly central role to improve prognosis accuracy and disease mechanisms,” Dr. Binette said.

Tau’s role in Alzheimer’s disease

Tau, along with amyloid-beta, is a key protein involved in Alzheimer’s disease.

Tau proteins in the brains of people with Alzheimer’s disease are misfolded and abnormally shaped. The normal tau protein forms part of a structure called a microtubule, which helps transport nutrients and other important substances from one part of the nerve cell to another. When tau proteins malfunction, they form tangles, which prevent the nerve cell from communicating properly and are a defining component of Alzheimer’s disease.

Recent Alzheimer’s Disease Research-funded studies have opened new avenues for measuring tau and underscore the importance of the protein’s role in detecting and preventing Alzheimer’s.

The tau-measuring PrecivityAD2 blood test from C2N Diagnostics, whose first iteration received critical early support from Alzheimer’s Disease Research, could facilitate a more accurate diagnosis of Alzheimer’s disease in its earlier stages at a reduced cost to patients.

Alzheimer’s Disease Research is also funding work on an innovative new blood test that detects a less frequently measured biomarker, brain-derived tau, of Alzheimer’s disease neurodegeneration in the blood. This advance could lead to earlier diagnosis of Alzheimer’s and could ultimately provide a noninvasive way to track neurodegeneration in real time, allowing health care providers to monitor Alzheimer’s progression and responsiveness to treatments.

Research published

Dr. Binette and her collaborators have published their findings in the scientific journals Nature Medicine and Nature Communications.

David Levine contributed to this article.