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Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 2/2019

21.10.2018 | Original Article

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

verfasst von: 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

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 2/2019

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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.
Literatur
1.
Zurück zum Zitat Reich DS, Lucchinetti CF, Calabresi PA. Multiple Sclerosis. N Engl J Med. 2018;378:169–80.CrossRef Reich DS, Lucchinetti CF, Calabresi PA. Multiple Sclerosis. N Engl J Med. 2018;378:169–80.CrossRef
2.
Zurück zum Zitat Lassmann H. Multiple sclerosis: Lessons from molecular neuropathology. Exp Neurol. 2014:2–7. Lassmann H. Multiple sclerosis: Lessons from molecular neuropathology. Exp Neurol. 2014:2–7.
3.
Zurück zum Zitat Franklin RJM, Ffrench-Constant C. Remyelination in the CNS: From biology to therapy. Nat Rev Neurosci. 2008:839–55. Franklin RJM, Ffrench-Constant C. Remyelination in the CNS: From biology to therapy. Nat Rev Neurosci. 2008:839–55.
4.
Zurück zum Zitat Filippi M, Paty DW, Kappos L, Barkhof F, Compston DAS, Thompson AJ, et al. Correlations between changes in disability and T2-weighted brain MRI activity in multiple sclerosis: A follow-up study. Neurology. 1995;45:255–60.CrossRef Filippi M, Paty DW, Kappos L, Barkhof F, Compston DAS, Thompson AJ, et al. Correlations between changes in disability and T2-weighted brain MRI activity in multiple sclerosis: A follow-up study. Neurology. 1995;45:255–60.CrossRef
5.
Zurück zum Zitat Stankoff B, Freeman L, Aigrot MS, Chardain A, Dollé F, Williams A, et al. Imaging central nervous system myelin by positron emission tomography in multiple sclerosis using [methyl-11C]-2-(4-methylaminophenyl)- 6-hydroxybenzothiazole. Ann Neurol. 2011;69:673–80.CrossRef Stankoff B, Freeman L, Aigrot MS, Chardain A, Dollé F, Williams A, et al. Imaging central nervous system myelin by positron emission tomography in multiple sclerosis using [methyl-11C]-2-(4-methylaminophenyl)- 6-hydroxybenzothiazole. Ann Neurol. 2011;69:673–80.CrossRef
6.
Zurück zum Zitat Bodini B, Louapre C, Stankoff B. Advanced imaging tools to investigate multiple sclerosis pathology. Presse Med. 2015:e159–e67. Bodini B, Louapre C, Stankoff B. Advanced imaging tools to investigate multiple sclerosis pathology. Presse Med. 2015:e159–e67.
7.
Zurück zum Zitat Payoux P. Salabert AS. New PET markers for the diagnosis of dementia. Curr Opin Neurol. 2017:608–16. Payoux P. Salabert AS. New PET markers for the diagnosis of dementia. Curr Opin Neurol. 2017:608–16.
8.
Zurück zum Zitat Matías-Guiu JA, Oreja-Guevara C, Cabrera-Martín MN, Moreno-Ramos T, Carreras JL, Matías-Guiu J. Amyloid proteins and their role in multiple sclerosis. Considerations in the use of amyloid-PET imaging. Front Neurol. 2016. Matías-Guiu JA, Oreja-Guevara C, Cabrera-Martín MN, Moreno-Ramos T, Carreras JL, Matías-Guiu J. Amyloid proteins and their role in multiple sclerosis. Considerations in the use of amyloid-PET imaging. Front Neurol. 2016.
9.
Zurück zum Zitat Bodini B, Veronese M, García-Lorenzo D, Battaglini M, Poirion E, Chardain A, et al. Dynamic Imaging of Individual Remyelination Profiles in Multiple Sclerosis. Ann Neurol. 2016;79:726–38.CrossRef Bodini B, Veronese M, García-Lorenzo D, Battaglini M, Poirion E, Chardain A, et al. Dynamic Imaging of Individual Remyelination Profiles in Multiple Sclerosis. Ann Neurol. 2016;79:726–38.CrossRef
10.
Zurück zum Zitat Matías-Guiu JA, Cabrera-Martín MN, Matías-Guiu J, Oreja-Guevara C, Riola-Parada C, Moreno-Ramos T, et al. Amyloid PET imaging in multiple sclerosis: an 18F-florbetaben study. BMC Neurol. 2015;15:243.CrossRef Matías-Guiu JA, Cabrera-Martín MN, Matías-Guiu J, Oreja-Guevara C, Riola-Parada C, Moreno-Ramos T, et al. Amyloid PET imaging in multiple sclerosis: an 18F-florbetaben study. BMC Neurol. 2015;15:243.CrossRef
11.
Zurück zum Zitat Grecchi E, O’Doherty J, Veronese M, Tsoumpas C, Cook GJ, Turkheimer FE. Multimodal Partial-Volume Correction: Application to 18F-Fluoride PET/CT Bone Metastases Studies. J Nucl Med. 2015;56:1408–14.CrossRef Grecchi E, O’Doherty J, Veronese M, Tsoumpas C, Cook GJ, Turkheimer FE. Multimodal Partial-Volume Correction: Application to 18F-Fluoride PET/CT Bone Metastases Studies. J Nucl Med. 2015;56:1408–14.CrossRef
12.
Zurück zum Zitat Glodzik L, Kuceyeski A, Rusinek H, Tsui W, Mosconi L, Li Y, et al. Reduced glucose uptake and Aβ in brain regions with hyperintensities in connected white matter. Neuroimage. 2014;100:684–91.CrossRef Glodzik L, Kuceyeski A, Rusinek H, Tsui W, Mosconi L, Li Y, et al. Reduced glucose uptake and Aβ in brain regions with hyperintensities in connected white matter. Neuroimage. 2014;100:684–91.CrossRef
13.
Zurück zum Zitat Glodzik L, Rusinek H, Li J, Zhou C, Tsui W, Mosconi L, et al. Reduced retention of Pittsburgh compound B in white matter lesions. Eur J Nucl Med Mol Imaging. 2015;42:97–102.CrossRef Glodzik L, Rusinek H, Li J, Zhou C, Tsui W, Mosconi L, et al. Reduced retention of Pittsburgh compound B in white matter lesions. Eur J Nucl Med Mol Imaging. 2015;42:97–102.CrossRef
14.
Zurück zum Zitat Mangiardi M, Crawford DK, Xia X, Du S, Simon-Freeman R, Voskuhl RR, et al. An animal model of cortical and callosal pathology in multiple sclerosis. Brain Pathol. 2011;21:263–78.CrossRef Mangiardi M, Crawford DK, Xia X, Du S, Simon-Freeman R, Voskuhl RR, et al. An animal model of cortical and callosal pathology in multiple sclerosis. Brain Pathol. 2011;21:263–78.CrossRef
15.
Zurück zum Zitat Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L. Axonal Transection in the Lesions of Multiple Sclerosis. N Engl J Med. 1998;338:278–85.CrossRef Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L. Axonal Transection in the Lesions of Multiple Sclerosis. N Engl J Med. 1998;338:278–85.CrossRef
16.
Zurück zum Zitat Gehrmann J, Banati RB, Cuzner ML, Kreutzberg GW, Newcombe J. Amyloid precursor protein (APP) expression in multiple sclerosis lesions. Glia. 1995;15:141–51.CrossRef Gehrmann J, Banati RB, Cuzner ML, Kreutzberg GW, Newcombe J. Amyloid precursor protein (APP) expression in multiple sclerosis lesions. Glia. 1995;15:141–51.CrossRef
17.
Zurück zum Zitat Hu X, Hicks CW, He W, Wong P, MacKlin WB, Trapp BD, et al. BACE1 modulates myelination in the central and peripheral nervous system. Nat Neurosci. 2006;9:1520–5.CrossRef Hu X, Hicks CW, He W, Wong P, MacKlin WB, Trapp BD, et al. BACE1 modulates myelination in the central and peripheral nervous system. Nat Neurosci. 2006;9:1520–5.CrossRef
18.
Zurück zum Zitat Augutis K, Axelsson M, Portelius E, Brinkmalm G, Andreasson U, Gustavsson MK, et al. Cerebrospinal fluid biomarkers of β-amyloid metabolism in multiple sclerosis. Mult Scler J. 2013;19:543–52.CrossRef Augutis K, Axelsson M, Portelius E, Brinkmalm G, Andreasson U, Gustavsson MK, et al. Cerebrospinal fluid biomarkers of β-amyloid metabolism in multiple sclerosis. Mult Scler J. 2013;19:543–52.CrossRef
19.
Zurück zum Zitat Mattsson N, Axelsson M, Haghighi S, Malmeström C, Wu G, Anckarsäter R, et al. Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis. Mult Scler. 2009;15:448–54.CrossRef Mattsson N, Axelsson M, Haghighi S, Malmeström C, Wu G, Anckarsäter R, et al. Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis. Mult Scler. 2009;15:448–54.CrossRef
20.
Zurück zum Zitat Mori F, Rossi S, Sancesario G, Codecá C, Mataluni G, Monteleone F, et al. Cognitive and cortical plasticity deficits correlate with altered amyloid-Β CSF levels in multiple sclerosis. Neuropsychopharmacology. 2011;36:559–68.CrossRef Mori F, Rossi S, Sancesario G, Codecá C, Mataluni G, Monteleone F, et al. Cognitive and cortical plasticity deficits correlate with altered amyloid-Β CSF levels in multiple sclerosis. Neuropsychopharmacology. 2011;36:559–68.CrossRef
21.
Zurück zum Zitat Gentile A, Mori F, Bernardini S, Centonze D. Role of amyloid-beta CSF levels in cognitive deficit in MS. Clin Chim Acta. 2015;449:23–30.CrossRef Gentile A, Mori F, Bernardini S, Centonze D. Role of amyloid-beta CSF levels in cognitive deficit in MS. Clin Chim Acta. 2015;449:23–30.CrossRef
22.
Zurück zum Zitat Pietroboni AM, Schiano Di Cola F, Scarioni M, Fenoglio C, Spanò B, Arighi A, et al. CSF β-amyloid as a putative biomarker of disease progression in multiple sclerosis. Mult Scler. 2017;23:1085–91.CrossRef Pietroboni AM, Schiano Di Cola F, Scarioni M, Fenoglio C, Spanò B, Arighi A, et al. CSF β-amyloid as a putative biomarker of disease progression in multiple sclerosis. Mult Scler. 2017;23:1085–91.CrossRef
23.
Zurück zum Zitat Pietroboni AM, Caprioli M, Carandini T, Scarioni M, Ghezzi L, Arighi A, et al. CSF β-amyloid predicts prognosis in patients with multiple sclerosis. Mult Scler J. 2018:135245851879170. Pietroboni AM, Caprioli M, Carandini T, Scarioni M, Ghezzi L, Arighi A, et al. CSF β-amyloid predicts prognosis in patients with multiple sclerosis. Mult Scler J. 2018:135245851879170.
24.
Zurück zum Zitat Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. Ann Neurol. 2011;69:292–302.CrossRef Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. Ann Neurol. 2011;69:292–302.CrossRef
25.
Zurück zum Zitat Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sørensen PS, Thompson AJ, et al. Defining the clinical course of multiple sclerosis: The 2013 revisions. Neurology. 2014:278–86. Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sørensen PS, Thompson AJ, et al. Defining the clinical course of multiple sclerosis: The 2013 revisions. Neurology. 2014:278–86.
26.
Zurück zum Zitat Kurtzke JF. Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology. 1983;33:1444.CrossRef Kurtzke JF. Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology. 1983;33:1444.CrossRef
27.
Zurück zum Zitat Bergamaschi R, Montomoli C, Mallucci G, Lugaresi A, Izquierdo G, Grand’Maison F, et al. BREMSO: A simple score to predict early the natural course of multiple sclerosis. Eur J Neurol. 2015;22:981–9.CrossRef Bergamaschi R, Montomoli C, Mallucci G, Lugaresi A, Izquierdo G, Grand’Maison F, et al. BREMSO: A simple score to predict early the natural course of multiple sclerosis. Eur J Neurol. 2015;22:981–9.CrossRef
28.
Zurück zum Zitat Goretti B, Patti F, Cilia S, Mattioli F, Stampatori C, Scarpazza C, et al. The Rao’s Brief Repeatable Battery version B: Normative values with age, education and gender corrections in an Italian population. Neurol Sci. 2014;35:79–82.CrossRef Goretti B, Patti F, Cilia S, Mattioli F, Stampatori C, Scarpazza C, et al. The Rao’s Brief Repeatable Battery version B: Normative values with age, education and gender corrections in an Italian population. Neurol Sci. 2014;35:79–82.CrossRef
29.
Zurück zum Zitat Schmidt P, Gaser C, Arsic M, Buck D, Förschler A, Berthele A, et al. An automated tool for detection of FLAIR-hyperintense white-matter lesions in Multiple Sclerosis. Neuroimage. 2012;59:3774–83.CrossRef Schmidt P, Gaser C, Arsic M, Buck D, Förschler A, Berthele A, et al. An automated tool for detection of FLAIR-hyperintense white-matter lesions in Multiple Sclerosis. Neuroimage. 2012;59:3774–83.CrossRef
30.
Zurück zum Zitat Fleisher AS, Chen K, Liu X, Roontiva A, Thiyyagura P, Ayutyanont N, et al. Using positron emission tomography and florbetapir F18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to Alzheimer disease. Arch Neurol. 2011;68:1404–11.CrossRef Fleisher AS, Chen K, Liu X, Roontiva A, Thiyyagura P, Ayutyanont N, et al. Using positron emission tomography and florbetapir F18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to Alzheimer disease. Arch Neurol. 2011;68:1404–11.CrossRef
31.
Zurück zum Zitat Mahad DH, Trapp BD, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol. 2015;14:183–93.CrossRef Mahad DH, Trapp BD, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol. 2015;14:183–93.CrossRef
Metadaten
Titel
Amyloid PET as a marker of normal-appearing white matter early damage in multiple sclerosis: correlation with CSF β-amyloid levels and brain volumes
verfasst von
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
Publikationsdatum
21.10.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 2/2019
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-018-4182-1

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