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Purpose <p>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.</p> Methods <p>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 (<i>n</i> = 58).</p> Results <p>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.</p> Conclusions <p>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.</p>

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

  • 期刊论文

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  • 发表日期：

    2026年5月27日

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  • Agostino Chiaravalloti,
  • Caterina Motta,
  • Chiara Giuseppina Bonomi,
  • Martina Poli,
  • Carmela Di Russo,
  • Orazio Schillaci,
  • Alessandro Martorana

摘要

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.