Alzheimer's Imaging Consortium.

Area of Science:

• Neuroimaging
• Radiochemistry
• Alzheimer's Disease Research

Background:

• Tau tangle deposition correlates with Alzheimer's disease (AD) clinical symptoms and cognitive decline.
• In vivo measurement of tau deposition is possible using positron emission tomography (PET).
• Extra-cerebral signal sources may bias tau PET quantification, but their impact is not well understood.

Purpose of the Study:

• Investigate off-target signal sources in tau PET imaging.
• Assess the impact of extra-cerebral signal on quantification using 18F-AV-1451 and 18F-MK-6240 tracers.
• Determine if skull and meninges contribute to off-target PET signal.

Main Methods:

• Acquired T1-weighted MRI, PiB amyloid PET, and tau PET scans for 42 participants.
• Quantified tau PET using SUV and SUVR with cerebellar grey as reference.
• Developed subject-specific skull and meningeal masks using CT and MNI-152 T1-weighted images to isolate extra-cerebral signal.

Main Results:

• Extra-cerebral off-target signal was more pronounced and widespread with 18F-MK-6240 compared to 18F-AV-1451.
• This signal was observed across the cortical surface and posterior cerebellum in both amyloid-negative and amyloid-positive individuals.
• The findings suggest potential bias in cerebellar reference region quantification for tau PET SUVR.

Conclusions:

• Both tau PET tracers exhibit extra-cerebral off-target signal, with 18F-MK-6240 showing a more pronounced and widespread presence.
• Subject-specific skull and meningeal masks can effectively isolate this signal for further analysis.
• Further research is needed to explore contributing factors like demographics, health, and genetics to this off-target signal.