Tau PET imaging can predict cognitive decline

Alzheimer’s disease, one of the most common neurodegenerative diseases, is characterised by the accumulation of neurotoxic proteins in the brain — namely amyloid plaques and tau tangles. Researchers from the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG) have now demonstrated that tau PET — a novel imaging technique for visualising the tau protein — can predict cognitive decline in patients much better than the imaging techniques normally used.

One of the main diagnostic tools for Alzheimer’s disease is positron emission tomography (PET), an imaging technique in which low-level radioactive tracers are injected to visualise specific pathological processes in the brain. As explained by UNIGE Associate Professor Valentina Garibotto, these tracers are “designed to bind to the human molecules that we want to detect, making them visible with the PET tomographs”.

“Specific tracers for amyloid exist … and tracers to monitor glucose metabolism, which indicates the brain’s ability to use its energy resources correctly, have long existed,” Garibotto continued. “However, Alzheimer’s disease is complex and these two techniques are not enough to provide all the answers.”

Flortaucipir, a radiotracer that binds to the tau protein, was approved by the US Food and Drug Administration (FDA) in 2020. It allows the detection of tau accumulation as well as its distribution in the brain to precisely assess its role in the clinical manifestation of the disease. Scientists from UNIGE and HUG wanted to determine which imaging modality — amyloid PET, glucose metabolism PET or tau PET — would best predict future cognitive decline due to Alzheimer’s disease, and so recruited around 90 participants from the HUG Memory Centre.

“Our results show that while the various PET measures were all associated with the presence of cognitive symptoms, confirming their role as strong indicators of Alzheimer’s disease, tau PET was the best to predict the rate of cognitive decline, even in individuals with minimal symptoms,” said Cecilia Boccalini, a PhD student in Garibotto’s team and first author of the study.

Amyloid plaques are not necessarily accompanied by cognitive or memory loss, but their absence or presence is the main determinant of whether a patient’s condition remains stable or deteriorates rapidly. It has previously been difficult to develop imaging techniques to visualise tau, mainly because of its lower concentration and particularly complex structure. The team’s results, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, are thus a strong argument in favour of incorporating tau PET into routine clinical evaluation to assess individual prognosis and select the most appropriate therapeutic strategy for each patient.

“This breakthrough is crucial for better management of Alzheimer’s disease,” Garibotto said. “Recently, drugs targeting amyloid have shown positive results. New drugs targeting the tau protein also look promising. By detecting the pathology as early as possible, before the brain is further damaged … we hope to be able to make a greater impact on patients’ future and quality of life.

“Similarly, we are beginning to map the distribution of tau in order to understand how its location in the different regions of the brain influences symptoms,” Garibotto added. Indeed, the causes and different stages of the disease are proving to be much less uniform than previously thought, and individual susceptibility to the same phenomena needs to be better understood.

Image caption: Tau imaging with 18F-Flortaucipir PET in Alzheimer’s disease. The figure shows a prototypical tau accumulation pattern, obtained by comparing tau load of patients with Alzheimer’s disease vs healthy controls. The blue-to-white colour scale indicates more pronounced tau loads, with pink-white areas representing those with the highest accumulation. Image ©UNIGE