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

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

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5 Citations (Scopus)

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.

Original languageEnglish
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Amyloid
Positron-Emission Tomography
Multiple Sclerosis
Cerebrospinal Fluid
Brain
Spinal Puncture
Neurologic Examination
Myelin Sheath
White Matter
Software
Biomarkers
Regression Analysis
Magnetic Resonance Imaging

Keywords

  • Amyloid
  • Amyloid tracer
  • Florbetapir
  • Multiple sclerosis
  • PET
  • White matter

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

@article{ab59eb40763e4d5fabf6c46c2de7c18d,
title = "Amyloid PET as a marker of normal-appearing white matter early damage in multiple sclerosis: correlation with CSF β-amyloid levels and brain volumes",
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.",
keywords = "Amyloid, Amyloid tracer, Florbetapir, Multiple sclerosis, PET, White matter",
author = "Pietroboni, {Anna M.} and Tiziana Carandini and Annalisa Colombi and Matteo Mercurio and Laura Ghezzi and Giovanni Giulietti and Marta Scarioni and Andrea Arighi and Chiara Fenoglio and {De Riz}, {Milena A.} and Fumagalli, {Giorgio G.} and Paola Basilico and Maria Serpente and Marco Bozzali and Elio Scarpini and Daniela Galimberti and Giorgio Marotta",
year = "2018",
month = "1",
day = "1",
doi = "10.1007/s00259-018-4182-1",
language = "English",
journal = "European Journal of Pediatrics",
issn = "0340-6199",
publisher = "Springer Berlin Heidelberg",

}

TY - JOUR

T1 - Amyloid PET as a marker of normal-appearing white matter early damage in multiple sclerosis

T2 - correlation with CSF β-amyloid levels and brain volumes

AU - Pietroboni, Anna M.

AU - Carandini, Tiziana

AU - Colombi, Annalisa

AU - Mercurio, Matteo

AU - Ghezzi, Laura

AU - Giulietti, Giovanni

AU - Scarioni, Marta

AU - Arighi, Andrea

AU - Fenoglio, Chiara

AU - De Riz, Milena A.

AU - Fumagalli, Giorgio G.

AU - Basilico, Paola

AU - Serpente, Maria

AU - Bozzali, Marco

AU - Scarpini, Elio

AU - Galimberti, Daniela

AU - Marotta, Giorgio

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Amyloid

KW - Amyloid tracer

KW - Florbetapir

KW - Multiple sclerosis

KW - PET

KW - White matter

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U2 - 10.1007/s00259-018-4182-1

DO - 10.1007/s00259-018-4182-1

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JO - European Journal of Pediatrics

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SN - 0340-6199

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