Biomarkers.

Area of Science:

• Neuroimaging
• Nuclear Medicine
• Alzheimer's Disease Research

Background:

• Tau tangle deposition correlates with Alzheimer's disease (AD) symptoms and cognitive decline.
• In vivo tau deposition is measurable using positron emission tomography (PET).
• Extra-cerebral signal (skull, meninges) may bias tau PET quantification, but its impact is unclear.

Purpose of the Study:

• To investigate off-target signal sources in individuals undergoing tau PET scans.
• To compare extra-cerebral signal between 18F-AV-1451 and 18F-MK-6240 tau PET tracers.
• To assess the impact of off-target signals on tau PET quantification in Alzheimer's disease research.

Main Methods:

• Acquired T1-weighted MRI, Pittsburgh Compound B (PiB) amyloid PET, and tau PET in 42 participants.
• Quantified tau PET using standardized uptake values (SUV) and SUV ratios (SUVRs) with cerebellar grey reference.
• Developed subject-specific masks for skull bone and meninges using CT and MNI-152 aligned tau PET images.

Main Results:

• Extra-cerebral off-target signal was more pronounced and widespread with 18F-MK-6240 compared to 18F-AV-1451.
• The 18F-MK-6240 signal affected the entire cortical surface and posterior cerebellum.
• This pronounced signal may impact cerebellar reference region-based tau PET SUVR quantification.

Conclusions:

• Both tau PET tracers exhibit off-target extra-cerebral signal, but it is more significant in 18F-MK-6240.
• Subject-specific skull and meningeal masks can help isolate and determine the cause of this signal.
• Further research is needed to explore demographic, health, and genetic factors contributing to this signal.