Alzheimer: Phosphorylation of Tau proteins leads to disintegration of microtubuli in a neuron axon
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Cognitive decline is best assessed by tau PET, according to new research from a University of Geneva (UNIGE) and Geneva University Hospitals (HUG) team. Their results, the researchers say, support incorporating tau PET into the routine clinical evaluation and provide patients with early and individualized care.

This work is published today in Alzheimer’s & Dementia, and the senior author is Valentina Garibotto, associate professor in the department of radiology and medical informatics at UNIGE Faculty of Medicine.

Alzheimer’s disease involves accumulation of neurotoxic proteins—amyloid plaques and tau tangles—in the brain. Due to the silent development of pathology over decades, very early diagnosis is crucial to be able to take action as early as possible in the disease process. One of the main diagnostic tools for this is positron emission tomography (PET), an imaging technique in which tracers are injected to visualize specific pathological processes in the brain.

“PET involves injecting patients with low-level radioactive tracers that disappear within a few hours. They are designed to bind to the human molecules that we want to detect, making them visible with the PET tomographs,” explains Garibotto.

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

Flortaucipir is a radiotracer that binds to the tau protein. It was approved by the Food and Drug Administration in 2020 and detects tau accumulation as well as its distribution in the brain to precisely assess the protein’s role in the clinical manifestation of the disease. Scientists from the UNIGE and the 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. Around 90 participants were recruited at the HUG Memory Center.

“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,” summarizes Cecilia Boccalini, a PhD student in Garibotto’s team and first author of this study.

Amyloid plaques are not necessarily accompanied by cognitive or memory loss. However, the presence of tau goes hand in hand with clinical symptoms. Its absence or presence is the main determinant of whether a patient’s condition remains stable or deteriorates rapidly. It has been more difficult to develop imaging techniques to visualize tau, mainly because of its lower concentration and particularly complex structure.

“This breakthrough is crucial for better management of Alzheimer’s disease. 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, and thanks to new treatments, we hope to be able to make a greater impact on patients’ future and quality of life,” Garibotto points out.

She adds that, “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.”

Since the causes and different stages of the disease are proving to be much less uniform than previously thought, the ability to assess individual susceptibility is more important.

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