Molecule That Binds to Tau and Works as Tracer Might Help to Diagnose and Treat Alzheimer’s, Study Reports

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A newly identified “tracer” molecule that binds to and “lights up” aggregates of tau — a protein linked to Alzheimer’s disease and related dementias – showed promise as a way to diagnose Alzheimer’s and measure the effectiveness of treatment in patients, researchers reported.

The study, “First in‐human PET study of 3 novel tau radiopharmaceuticals: [11C]RO6924963, [11C]RO6931643, and [18F]RO6958948,” was published in The Journal of Nuclear Medicine.

Alzheimer’s disease is characterized by the presence of abnormal protein aggregates — amyloid plaques and tau tangles — in the brain. A hurdle in diagnosing Alzheimer’s disease has been the inability to examine the real-time generation of these aggregates in the brains of living patients.

“One of the greatest public health challenges is Alzheimer’s disease, for which there currently is no cure and no definitive diagnostic until autopsy,” Dean Wong, MD, PhD, a professor at the Johns Hopkins University School of Medicine and lead author of the research article, said in a press release. “We have been working hard to identify new radiopharmaceuticals that can help speed the discoveries of diagnostics and treatments for these devastating neurodegenerative disorders.”

Researchers investigated the capacity of a novel tracer to identify tau aggregates in patients’ brains using positron emission tomography (PET), a medical imaging technique that is used to observe metabolic processes in the body as a diagnostic aid.

The team had previously identified three promising tracers from a collection of about 550 potential molecules. The researchers tested these three tracers in nonhuman primates, and results showed that the molecules were safe and promising enough to test in patients.

In this study, they compared the imaging properties of the three novel tau PET tracers in human subjects, and based on that comparison, selected one tracer most suitable for application in clinical research for further evaluation.

A total of 12 Alzheimer’s patients (all age 50 or older) and 12 healthy people serving as a control group were recruited for brain-only PET scans; among controls, seven were 25-38 years old and five were 50 or older. An additional six older healthy people were recruited for full-body scanning.

The study was divided into three parts. In part one, each individual was injected with two of the three tracers prior to undergoing a brain PET scan. The team then evaluated if each of the three tracers were taken up by the brain safely and effectively in Alzheimer’s disease and in young healthy subjects, and which was best imaged by PET.

The best tracer, [18F]RO948, showed excellent brain uptake. It was then used in part two, where five patients and five older controls underwent additional brain imaging and whole-body radiation dosimetry — which calculates and assesses the radiation dose absorbed by the human body.

In part three, four of the Alzheimer’s patients who participated in parts one and two returned for repeat PET scans of [18F]RO-948, with no intervening tau- or amyloid-targeted treatment, to give a preliminary idea of the progression of tau aggregate production. The range of times between scans was 6.2 months to 21.6 months (mean 16.9 months).

Little or no tracer was found in the brains of healthy controls viewed through the scans. Those of Alzheimer’s patients, however, showed the tracer — and tau — in brain regions consistent with what has been reported in postmortem studies into tau tangles in patients (particularly, the brain’s temporal lobe, parietal lobe and occipital lobe).

These findings support [18F]RO-948 as a possibly promising radio-tracer for diagnostic imaging of tau aggregates in the brains of Alzheimer’s patients and those suspected of having the disease.

“It is our hope that tools such as [18F]RO-948 will allow us to gain a better understanding of the pathophysiology of Alzheimer’s disease, and in the context of drug development select patients for clinical trials, confirm the mechanism of action of drugs targeting pathological tau, and monitor the effects of disease modifying therapies regardless of whether or not they target tau directly,” the researchers concluded.

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