New tau PET tracer carries potential to advance Alzheimer's testing

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 - Tau-in-an-AD-brain
Strong binding of tau ligand in an AD patient.
Source: Neuron

There’s a new way to detect the buildup of tau proteins in living brains, according to  research published in the journal  Brain. The method uses PET imaging to see in which regions of the brain the protein is accumulating. It may also possibly reveal clues about the potential for Alzheimer’s or other tau-related cognitive diseases in individual patients—and pave the way for new types of Alzheimer’s drugs.

“These tracers, along with PET tracers revealing extracellular plaques containing amyloid-β fibrils, will be essential for improving the early diagnosis of Alzheimer’s disease in clinical practice as well as in the evaluation of novel disease-modifying therapies,” the study authors wrote.

This study focused on people who had a gene mutation causing a pathology related to tau proteins and not beta amyloid proteins in order focus more singularly on the tau PET tracer. The participants were all had that particular mutation and were from Sweden, ages 56, 60 and 76, and the younger two (A and B) had slow-moving mild cognitive impairment while the older (C) had fully developed dementia. There were also four control subjects and five participants with Alzheimer’s disease.

According to the researchers, this was the first study of its kind, to track a tau PET tracer’s degree of appearance in a live person and then have it compared to actual tau incidence in a post-mortem exam.

The PET tracer F-AV-1451 was most detected in the temporal lobes, the hippocampus and the anterior of the inferior temporal gyrus in patients A and B. In patient C, it was found mostly in the temporal lobes, the basal ganglia and the frontal lobes, with no detection in the parietal or occipital lobes. The tracer was not found in the cortical areas of the brain in the control participants.

And in patients A and B, the researchers found a significant inverse relationship between the F-AV-1451 detection and a later F-FDG scan.

The researchers were able to compare the PET scans of patient C with immunohistochemical analysis of the person’s brain after death, because the participant died just two weeks after the PET scan. In that exam, staining showed “extensive” incidence of tau protein in the temporo-limbic region of the brain, the anterior temporal lobe and the hippocampus. There was low-grade and minor tau pathology detected in the frontal cortical areas and the posterior cortical areas, respectively.

These post-mortem findings were significantly correlated to the PET tau detection when patient C was alive.

Based on the PET scans and the post-mortem exam, the researchers conclude that using F-AV-1451 on a live person’s brain is a reliable and useful way to find out where an excess of tau proteins might be accumulating in that brain and how that could affect their cognition or behavior. In the future, understanding how tau protein accumulation and cognition and behavior are correlated could help researchers find ways to develop. This advancement may allow for testing new drugs for Alzheimer’s disease and other types of dementia.

"There are new candidate drugs which aim to reduce the accumulation of tau. The imaging method opens up opportunities to investigate the development of the disease at a detailed level, and to observe how tau aggregates are affected by the drugs,” researcher Ruben Smith, MD, PhD said in a statement