Related Experiment Video
Updated: May 28, 2026
Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451
Published on: April 18, 2025
Plasma phosphorylated tau biomarkers map onto [^18F]FDG PET hypometabolism: a voxel-wise study in a clinical cohort
Agostino Chiaravalloti1,2, Caterina Motta3, Chiara Giuseppina Bonomi3
1Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy. agostino.chiaravalloti@uniroma2.it.
Purpose:
To examine voxel-wise associations between plasma phosphorylated tau biomarkers and cerebellum-normalised [^18F]fluorodeoxyglucose ([^18F]FDG) positron emission tomography (PET) uptake in cognitively impaired patients, and whether these associations persist in a cerebrospinal fluid (CSF)-confirmed Alzheimer's disease (AD) subgroup.
Methods:
One hundred consecutive patients who underwent brain [^18F]FDG PET and plasma biomarker assessment within ≤ 6 months were included. Images were spatially normalised, smoothed, and divided voxel-wise by a subject-specific bilateral cerebellar reference value derived from Automated Anatomical Labelling 3 (AAL3) cerebellar regions. Voxel-wise multiple regressions tested associations with plasma Aβ42/Aβ40, p-tau181, p-tau181/Aβ42, p-tau217, and p-tau217/Aβ42, adjusting for age and sex, in the full cohort and the CSF-confirmed AD subgroup (n = 58).
Results:
In the full cohort, plasma p-tau181 and p-tau181/Aβ42 showed negative associations with cerebellum-normalised [^18F]FDG uptake, predominantly in bilateral ventral temporal/fusiform regions. The strongest and most spatially consistent finding involved p-tau181/Aβ42. Plasma Aβ42/Aβ40 and p-tau217 showed no suprathreshold associations, whereas p-tau217/Aβ42 showed only a small focal cluster. In the CSF-confirmed AD subgroup, p-tau181/Aβ42 remained the most consistent tau-related marker, showing negative associations with cerebellum-normalised [^18F]FDG uptake in temporal/temporo-limbic and posterior cortical regions, whereas p-tau217 and p-tau217/Aβ42 showed no suprathreshold clusters.
Conclusions:
After voxel-wise cerebellar normalisation, plasma p-tau181/Aβ42 showed the most robust association with [^18F]FDG PET hypometabolism, predominantly involving bilateral ventral temporal/fusiform regions in the full cohort and temporal/temporo-limbic and posterior cortical regions in the CSF-confirmed AD subgroup. The heterogeneous full-cohort findings may partly reflect AD-versus-non-AD biological separation. Overall, plasma tau biomarkers and [^18F]FDG PET provide complementary molecular and metabolic information.
