ArticleEuropean journal of nuclear medicine and molecular imaging2026
Plasma phosphorylated tau biomarkers map onto [^18F]FDG PET hypometabolism: a voxel-wise study in a clinical cohort with CSF-confirmed AD subgroup analysis.
Article in European journal of nuclear medicine and molecular imaging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeTo 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.
methodsOne 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).
resultsIn 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.
conclusionsAfter 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.
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