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Amyloid PET as a marker of normal-appearing white matter early damage in multiple sclerosis: correlation with CSF β-amyloid levels and brain volumes

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Abstract

Purpose

The disease course of multiple sclerosis (MS) is unpredictable, and reliable prognostic biomarkers are needed. Positron emission tomography (PET) with β-amyloid tracers is a promising tool for evaluating white matter (WM) damage and repair. Our aim was to investigate amyloid uptake in damaged (DWM) and normal-appearing WM (NAWM) of MS patients, and to evaluate possible correlations between cerebrospinal fluid (CSF) β-amyloid1-42 (Aβ) levels, amyloid tracer uptake, and brain volumes.

Methods

Twelve MS patients were recruited and divided according to their disease activity into active and non-active groups. All participants underwent neurological examination, neuropsychological testing, lumbar puncture, brain magnetic resonance (MRI) imaging, and 18F-florbetapir PET. Aβ levels were determined in CSF samples from all patients. MRI and PET images were co-registered, and mean standardized uptake values (SUV) were calculated for each patient in the NAWM and in the DWM. To calculate brain volumes, brain segmentation was performed using statistical parametric mapping software. Nonparametric statistical analyses for between-group comparisons and regression analyses were conducted.

Results

We found a lower SUV in DWM compared to NAWM (p < 0.001) in all patients. Decreased NAWM-SUV was observed in the active compared to non-active group (p < 0.05). Considering only active patients, NAWM volume correlated with NAWM-SUV (p = 0.01). Interestingly, CSF Aβ concentration was a predictor of both NAWM-SUV (r = 0.79; p = 0.01) and NAWM volume (r = 0.81, p = 0.01).

Conclusions

The correlation between CSF Aβ levels and NAWM-SUV suggests that the predictive role of β-amyloid may be linked to early myelin damage and may reflect disease activity and clinical progression.

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Acknowledgements

This research was supported by Fondazione Monzino and the Italian Ministry of Health (“Ricerca Corrente” to ES). GGF was supported by the Associazione Italiana Ricerca Alzheimer ONLUS (AIRAlzh Onlus)-COOP Italia.

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Author notes

  1. Anna M. Pietroboni, Tiziana Carandini, Daniela Galimberti, and Giorgio Marotta contributed equally to this work.

Authors and Affiliations

  1. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy

    Anna M. Pietroboni, Tiziana Carandini, Annalisa Colombi, Matteo Mercurio, Laura Ghezzi, Marta Scarioni, Andrea Arighi, Milena A. De Riz, Giorgio G. Fumagalli, Paola Basilico, Elio Scarpini, Daniela Galimberti & Giorgio Marotta

  2. University of Milan, Milan, Italy

    Anna M. Pietroboni, Tiziana Carandini, Annalisa Colombi, Laura Ghezzi, Marta Scarioni, Andrea Arighi, Chiara Fenoglio, Milena A. De Riz, Giorgio G. Fumagalli, Paola Basilico, Maria Serpente, Elio Scarpini, Daniela Galimberti & Giorgio Marotta

  3. Dino Ferrari Center, Milan, Italy

    Anna M. Pietroboni, Tiziana Carandini, Annalisa Colombi, Laura Ghezzi, Marta Scarioni, Andrea Arighi, Milena A. De Riz, Giorgio G. Fumagalli, Paola Basilico, Elio Scarpini & Daniela Galimberti

  4. Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy

    Giovanni Giulietti & Marco Bozzali

  5. Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy

    Giorgio G. Fumagalli

  6. Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, UK

    Marco Bozzali

Authors
  1. Anna M. Pietroboni
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  2. Tiziana Carandini
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  3. Annalisa Colombi
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  4. Matteo Mercurio
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  5. Laura Ghezzi
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  6. Giovanni Giulietti
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  7. Marta Scarioni
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  8. Andrea Arighi
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  9. Chiara Fenoglio
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  10. Milena A. De Riz
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  11. Giorgio G. Fumagalli
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  12. Paola Basilico
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Corresponding author

Correspondence to Anna M. Pietroboni.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Pietroboni, A.M., Carandini, T., Colombi, A. et al. Amyloid PET as a marker of normal-appearing white matter early damage in multiple sclerosis: correlation with CSF β-amyloid levels and brain volumes. Eur J Nucl Med Mol Imaging 46, 280–287 (2019). https://doi.org/10.1007/s00259-018-4182-1

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