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

• Published in: European journal of nuclear medicine and molecular imaging Vol. 46; no. 2; pp. 280 - 287
• Main Authors: Pietroboni, Anna M., Carandini, Tiziana, Colombi, Annalisa, Mercurio, Matteo, Ghezzi, Laura, Giulietti, Giovanni, Scarioni, Marta, Arighi, Andrea, Fenoglio, Chiara, De Riz, Milena A., Fumagalli, Giorgio G., Basilico, Paola, Serpente, Maria, Bozzali, Marco, Scarpini, Elio, Galimberti, Daniela, Marotta, Giorgio
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-02-2019; Springer Nature B.V
• Subjects: Adult; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Biomarkers; Brain; Brain damage; Brain mapping; Cardiology; Cerebrospinal fluid; Correlation; Damage assessment; Disease Progression; Emission analysis; Female; Humans; Image processing; Image segmentation; Imaging; Magnetic resonance imaging; Male; Mathematical analysis; Measuring techniques; Medicine; Medicine & Public Health; Middle Aged; Multiple sclerosis; Multiple Sclerosis - diagnostic imaging; Multiple Sclerosis - metabolism; Multiple Sclerosis - pathology; Myelin; Neuroimaging; Nuclear Medicine; Oncology; Original Article; Orthopedics; Patients; Positron emission; Positron emission tomography; Positron-Emission Tomography - standards; Psychology; Radiology; Reference Values; Regression analysis; Statistical analysis; Statistical methods; Statistics; Substantia alba; Tomography; Tracers; White Matter - diagnostic imaging; White Matter - metabolism; White Matter - pathology; Young Adult; β-Amyloid; Multiple sclerosis; Amyloid; Florbetapir; Amyloid tracer; White matter; PET
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-018-4182-1

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-amyloid
1-42
(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
18
F-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.