What does this research mean for the field?

Plasma p-tau181/Aβ42 exhibits the most robust association with [^18F]FDG PET hypometabolism among plasma biomarkers in cognitively impaired patients, including those with CSF-confirmed Alzheimer's disease. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to explore the connections between plasma phosphorylated tau biomarkers and brain metabolism in cognitively impaired patients, focusing on those with confirmed Alzheimer’s disease (AD).

May 28, 2026European Journal of Nuclear Medicine and Molecular Imaging0 citationsOpen Access

Plasma phosphorylated tau biomarkers map onto ¹8FFDG PET hypometabolism: a voxel-wise study in a clinical cohort with CSF-confirmed AD subgroup analysis

ACAgostino ChiaravallotiUniversity of Rome Tor Vergata CMCaterina MottaUniversity of Rome Tor Vergata CBChiara Giuseppina BonomiPoliclinico Tor Vergata

Key Points

This research aims to explore the connections between plasma phosphorylated tau biomarkers and brain metabolism in cognitively impaired patients, focusing on those with confirmed Alzheimer’s disease (AD).
Analyzed data from 100 patients who had brain [^18F]FDG PET scans and plasma biomarker assessments within six months.
Performed voxel-wise multiple regression analyses to assess associations, adjusting for age and sex.
Conducted subgroup analyses for 58 patients with cerebrospinal fluid (CSF)-confirmed AD.
In the full cohort, plasma p-tau181 and p-tau181/Aβ42 showed negative associations with cerebellum-normalised [^18F]FDG uptake, especially in ventral temporal regions.
The strongest association was with p-tau181/Aβ42, while other biomarkers did not show significant associations.
In the CSF-confirmed AD subgroup, p-tau181/Aβ42 consistently correlated with decreased [^18F]FDG uptake in multiple brain areas.

Abstract

Abstract Purpose To examine voxel-wise associations between plasma phosphorylated tau biomarkers and cerebellum-normalised ¹8Ffluorodeoxyglucose (¹8FFDG) 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 ¹8FFDG 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 ¹8FFDG 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 ¹8FFDG 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 ¹8FFDG 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 ¹8FFDG PET provide complementary molecular and metabolic information.

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