Imagine being a detective, trying to solve a complex puzzle without any clues. That’s what it’s like for scientists studying Alzheimer’s disease and other tauopathies. Thankfully, they have an important tool in their arsenal: positron emission tomography (PET) imaging. PET scans allow researchers to see the molecular changes happening in the brains of patients with high precision. This article explores the different types of PET tracers used to detect amyloid-β (Aβ) and tau, two proteins implicated in Alzheimer’s disease and primary tauopathies. By understanding how these tracers work, scientists can better diagnose and monitor the progression of these diseases. However, there are challenges along the way, such as off-target binding of tracers to unrelated structures in the brain. Researchers are developing new generation tau PET tracers to improve binding properties and eliminate this confounding factor. The future looks hopeful as scientists continue to push the boundaries of imaging technology to unlock the mysteries of Alzheimer’s disease and other tauopathies. If you’re curious to learn more, dive into the fascinating research behind this article.

The detection and staging of Alzheimer’s disease (AD) using non-invasive imaging biomarkers is of substantial clinical importance. Positron emission tomography (PET) provides readouts to uncover molecular alterations in the brains of AD patients with high sensitivity and specificity. A variety of amyloid-β (Aβ) and tau PET tracers are already available for the clinical diagnosis of AD, but there is still a lack of imaging biomarkers with high affinity and selectivity for tau inclusions in primary tauopathies, such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Pick’s disease (PiD). This review aims to provide an overview of the existing Aβ and tau PET imaging biomarkers and their binding properties from in silico, in vitro, and in vivo assessment. Imaging biomarkers for pathologic proteins are vital for clinical diagnosis, disease staging and monitoring of the potential therapeutic approaches of AD. Off-target binding of radiolabeled tracers to white matter or other neural structures is one confounding factor when interpreting images. To improve binding properties such as binding affinity and to eliminate off-target binding, second generation of tau PET tracers have been developed. To conclude, we further provide an outlook for imaging tauopathies and other pathological features of AD and primary tauopathies.

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