A group of Japanese scientists have recently developed a pioneering brain imaging technique, capable of detecting a protein structure that accumulates in vast quantities inside the brain of Alzheimer’s patients.
The danger of tau protein
The protein in question is called tau. Under normal circumstances, tau serves great functional purpose, regulating neurite growth, organizing transport throughout neuronal cells, and is a component of the
cytoskeletal system. Tau is primarily found in neuronal cells of the central nervous system and provides stability for long projections called axons, which are used during transmission of electrical signals from cell to cell.
The precise mechanisms of pathology are poorly understood in the diseased brains of Alzheimer patients; however, advances in our understanding of some of the intricate processes of disease progression are beginning to be made.
There are two broad hypotheses that attempt to explain the basis for Alzheimer’s, involving tauopathies and amyloidopathies.
During Alzheimer’s the structure of the tau protein changes, as it becomes phosphorylated. Prominent researchers believe this could be caused by aberrations in the enzyme that catalyzes this reaction, alongside inflammatory processes and oxidative stress.
Once the tau undergoes this physical change it detaches from transport microtubules. Individual subunits of tau then aggregate to form disorganized deposits, called neurofibrillary tangles. In turn, this disrupts movement of substances along the axons of the neuron, ultimately, leading to cellular death.
The tau scan
The latest technology, which has been reported in the Sep. 18 issue of the journal Neuron, is thought to be capable of tracking Alzheimer’s disease progression. A simple scan identifies bundles of the hazardous tau protein, which typically aggregates within a region of the brain known as the hippocampus.
The team, led by the National Institute of Radiological Sciences, used positron emission tomography scans to compile a 3-dimensional image of tau in the brain. This technique is a nuclear medical imaging device, which creates images of the body by detecting pairs of gamma rays emitted from a tracer compound.
Although the actual technology has been around for some time, it is only now that researchers have recently managed to identify groups of imaging agents capable of visualizing tau.
The group tested their new tracers in mouse models and human participants. After developing fluorescent compounds, called PBBs, that affix to tau structures, PET scans were used to demonstrate the relationship between the deterioration in Alzheimer sufferers, relative to the presence of tangles of tau.
Dr. Makoto Higuchi, the senior author of the paper, discussed the advantages of the imaging technique in a recent press release:
“PET images of tau accumulation are highly complementary to images of senile amyloid beta plaques and provide robust information on brain regions developing or at risk for tau-induced neuronal death.”
Higuchi then goes on to explain that the presence of tau tangles is more suggestive of neuronal loss than senile plaques, containing beta amyloid.
The technique has also been used before by other researchers. For example, Wei Zhang and colleagues submitted a paper, entitled A Highly Selective and Specific PET Tracer for Imaging of Tau Pathologies, which studied the use of an 18F-labelled tracer compound. The group revealed that this tracer was rapidly uptaken in the brains of rodent models and demonstrated high binding affinity for tau tangles.
Future implications of the study
This scan could represent a huge step forward in the diagnosis of Alzheimer’s disease, as well as our ability to monitor its progression and severity. Currently, diagnosis of the disease is reliant upon use of a series of fallible neuropsychological and clinical examinations. An unfortunate consequence of this is that a 100% accurate diagnosis cannot be achieved until the brain is investigated at autopsy.
Aside from this, the PBB tracer-based PET scan could also be implemented in future research studies to highlight the impact of a particular drug on the development of tangles.
According to ITV News, Dr. Eric Karran, the director of research at Alzheimer’s Research UK, proclaims the study to be “promising,” but also calls for further research studies to determine the technique’s long-term viability. Nonetheless, with the development of new drugs, specifically designed to hone in on tau protein, Kerran believes these novel scans could demonstrate treatment efficacy during clinical trials.
Of course, there are other factors at play. The tauopathy mechanism is one of many proposed hypotheses and, therefore, it fails to explain Alzheimer’s disease in its entirety. However, the mere notion of a non-invasive brain scan to monitor the devastating effects of Alzheimer’s is a huge step forward and could represent a pioneering tool for both research and clinical study.
By: James Fenner