Can a new PET imaging tracer distinguish different tau diseases?
A new brain scanning chemical successfully maps and tells apart two different types of degenerative brain disorders based on where protein tangles build up.
Source
18F-AV-1451 positron emission tomography in Alzheimer's disease and progressive supranuclear palsy
What they did
The researchers scanned 19 patients with progressive supranuclear palsy, nine patients with Alzheimer's disease, six patients with mild cognitive impairment who had positive amyloid biomarker scans, and thirteen healthy controls using a PET tracer to map tau protein deposits in the brain. They also analyzed post-mortem brain tissues from three deceased donors—one with Alzheimer's, one with progressive supranuclear palsy, and one healthy control—to compare the scan results with physical brain samples.
What they found
The scans differentiated patients with Alzheimer's from those with progressive supranuclear palsy with 94.1% accuracy, showing high tracer binding in cortical regions for Alzheimer's and in the midbrain and basal ganglia for progressive supranuclear palsy. However, post-mortem analyses revealed that while the tracer bound specifically to the classic tau tangles of Alzheimer's, its binding in progressive supranuclear palsy and healthy control tissues was largely non-specific and off-target.
The limits
What it doesn't show
This study was cross-sectional, meaning it cannot demonstrate how the tracer's binding changes over time or how it would react to treatments. Furthermore, the findings are limited by the small sample sizes, particularly in the Alzheimer's and mild cognitive impairment groups. The study also could not identify the specific molecules causing the off-target tracer binding observed in the basal ganglia, which occurred even though post-mortem analysis showed no neuromelanin-containing cells there.
Key terms
- Tau protein
- A protein that normally stabilizes structures in brain cells but can misfold and clump together in neurodegenerative diseases.
- 18F-AV-1451
- A radioactive imaging agent used in PET scans to detect and map tau protein aggregates in the living human brain.
- Progressive supranuclear palsy
- A rare, progressive brain disorder that affects movement, balance, vision, and speech, characterized by a specific type of tau protein buildup.
- Positron emission tomography
- An imaging technique that uses radioactive substances to visualize metabolic and chemical processes in the body.
- Support vector machine
- A type of computer algorithm used in machine learning to classify data, such as sorting brain scans into diagnostic groups.
- Off-target binding
- A phenomenon where an imaging chemical attaches to unintended proteins or structures rather than its main target.
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Quiz yourself
What type of tau filaments are characteristically associated with Alzheimer's disease versus progressive supranuclear palsy (PSP)?
Common questions
How does the tracer distinguish between Alzheimer's and progressive supranuclear palsy?
It reveals different regional patterns: Alzheimer's shows high binding in outer cortical areas like the temporal lobe, whereas progressive supranuclear palsy shows high binding in deeper subcortical areas like the midbrain.
Does this PET scan work as a diagnostic tool in the clinic right now?
While the scan separated the groups with high accuracy in this study, it is not yet a standard diagnostic tool because it requires larger clinical trials and further validation of its off-target binding.
What is off-target binding and why is it a problem?
Off-target binding occurs when the tracer sticks to unintended parts of the brain, which can create false signals and make it difficult to know if the scan is truly measuring disease-related tau.
Why did the researchers look at post-mortem brain tissue?
They analyzed deceased tissues to physically verify whether the tracer was actually binding to tau protein structures or if it was attaching to other elements in the brain.
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