Published: 20-04-2016 21:41 | Updated: 22-04-2016 23:43

Imaging of tau protein holds promise in Alzheimer’s disease

New research illustrates the ability of Positron Emission Tomography (PET) imaging to map, in the living patient, the tau protein, one of the proteins that abnormally accumulates in the brain of patients with Alzheimer’s disease (AD) and some other dementias. Hopefully this method could be used to diagnose accurately dementia at an early stage, follow the pathological development in the living patient and evaluate treatments.

Professor Agneta Nordberg led the study authored by Konstantinos Chiotis, PhD student, and Laure Saint-Aubert, postdoctoral fellow, from the Division of Translational Alzheimer Neurobiology, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.

Alzheimer’s disease is characterized by the presence of two abnormally accumulated proteins in the brains of the affected patients, namely amyloid-beta and tau. Until recently, the assessment of the presence of those proteins has been only possible after death.

In the study ’Imaging in vivo tau pathology in Alzheimer's disease with THK5317 PET in a multimodal paradigm’, the scientists not only visualized the distribution of tau during life, but they also achieved to provide information regarding its relationship with the distribution of other key markers of Alzheimer’s disease, e.g. amyloid-beta aggregates and dysfunction of neuronal cells. The study was performed in collaboration with the Geriatric clinic at Karolinska University Hospital and Uppsala PET centre, and was published on March 21st 2016 in the European Journal of Nuclear Medicine and Molecular Imaging.

Novel tracer plays key role

The scientist aimed to develop a technique for imaging tau protein in Alzheimer’s disease patients with a novel specific tracer (THK5317). 33 individuals at different stages of Alzheimer’s disease, other dementias, as well as healthy volunteers were recruited and underwent PET scanning with the tau tracer THK5317, as well as tracers targeting amyloid-beta protein (PIB) and activity of neuronal cells (FDG).

PET imaging. Agneta Nordberg Group, Division of Translational Alzheimer Neurobiology ”The patients with Alzheimer’s disease showed high signal of the tau tracer in contrast to the healthy volunteers, illustrating that tau PET imaging could provide a useful tool for easily identifying the presence of pathology during life. The presence of tau was evident even in patients experiencing mild cognitive symptoms, highlighting that tau involvement could occur early in Alzheimer’s disease”, says Konstantinos Chiotis.

Further, the spatial distribution of tau was different from that of amyloid-beta protein or of dysfunctional neuronal cells, highlighting that the different processes are affecting different areas of the brain at different time points. Of note, in some areas of the brain of the patients, the presence of amyloid-beta was associated with that of tau indicating a possible interaction between the two proteins.

Evidence of tau aggregation was also found in the brains of patients suffering from other dementia syndromes, with different distribution from that observed in AD, indicating the potential utility of this tracer in differentiating neurodegenerative diseases.

Positron Emission Tomography markers in Alzheimer’s disease

PET, which allows to image functional processes of the human body, gave great boost to the field by providing tools for both diagnosing more accurately as well as understanding the evolution of the disease in the living patient. The patients are injected a radioactive pharmaceutical called a tracer, and scanned in a machine (PET camera). This low radiation dose technique (lower radiation than a simple computerized tomography; CT) enables us to image potentially each molecule in our bodies as long as a tracer for this specific molecule is available.

The Nordberg group earlier pioneered in the first amyloid-beta PET imaging and since then several amyloid PET tracers have been developed as well as approved for clinical use and constitute now important early diagnostic tools at large academic memory clinics such as the Karolinska University Hospital in Huddinge.

"Although we are still at an early stage of tau PET imaging development, this unique tool offers a great opportunity; to study in the living patient the full spectrum of the underlying pathology. These tracers could ensure the early and accurate diagnosis of dementias, the monitoring of the evolution of the diseases over time as well as the evaluation of the effect of potential disease modifying therapies that are becoming available", says Agneta Nordberg.

Funding

This study was financially supported by the Swedish Research Council (project 05817), Swedish Brain Power, Regional Agreement on Medical Training and Clinical Research (ALF) for Stockholm County Council, Strategic Research Program in Neuroscience at Karolinska Institutet, Foundation for Old Servants, Gun and Bertil Stohne’s Foundation, KI Foundations, Swedish Brain Foundation, Swedish Alzheimer’s Foundation (Alzheimerfonden), Demensfonden, Wenner-Gren Foundations, the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° HEALTH-F2-2011-278850 (INMiND), and the Swedish Foundation for Strategic Research (SSF).