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

word count: 250 Text word count: 2894 2 ABSTRACT Purpose: The disease course of multiple sclerosis (MS) is unpredictable and reliable prognostic biomarkers are needed. Positron emission tomography (PET) with β-amyloidtracers is a promising tool to evaluate white matter (WM) damage and repair. Our aims were 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 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 with statistical parametric mapping software was performed. Non-parametric 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.A decreased NAWM-SUV in active compared to non-active group was observed (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 myelin early damage and may reflect the disease activity and the clinical progression.

A new frontier for amyloid PET imaging: multiple sclerosis

“…Finally, in this group of patients, CSF Aβ concentration was a predictor of both NAWM SUV and NAWM volume. The correlation between CSF Aβ levels and NAWM SUV was considered by the authors to support the value of βamyloid in predicting early myelin damage [25].…”

“…However, given its short half-life, 11 C-PiB cannot be made available commercially. More recently, AMY-PET imaging with fluorinated tracers has been used to image demyelination in vivo in baboons, healthy subjects and small groups of MS patients [24,25]. From a clinical trial perspective, the availability of fluorinated AMY-PET tracers (with their longer halflife) already used in dementia diagnosis, may make the use of AMY-PET in tissue repair studies a realistic possibility.…”

“…In a study published in this issue of EJNMMI, Pietroboni et al investigated amyloid uptake in damaged WM (DWM) and NAWM in MS patients, and evaluated correlations among cerebrospinal fluid (CSF) β-amyloid1-42 (Aβ) levels, uptake of a fluorinated AMY-PET tracer ( 18 F-florbetapir) and brain volumes [25]. Twelve MS patients were recruited and stratified according to the evidence of disease activity in the previous year (i.e.…”

Changes of central noradrenaline transporter availability in immunotherapy-naïve multiple sclerosis patients

“…Previous PET studies in multiple sclerosis focused on neuroinflammation by measuring translocator protein or adenosine receptors to detect activated microglia 21,22 , on neurodegeneration by assessing glucose and choline metabolism, on myelin content targeting myelin sheaths [23][24][25] , or lately, on synaptic density 26 . Our hypothesis of changes in noradrenergic signalling in MS patients was based on a wealth of data from preclinical models 6,27 , some clinical studies 28,29 and our earlier finding of altered serotonin transporter availability in limbic and paralimbic regions of MS patients, which relates to psychometric measures of depression and fatigue 30 .…”

Molecular imaging of multiple sclerosis: from the clinical demand to novel radiotracers

“…To date amyloid PET studies in patients with MS have been carried out with [ 18 F] florbetapir and [ 18 F] florbetaben (Fig. 2b-c, respectively) (Matías-Guiu et al 2015; Pietroboni et al 2019). In the study from Matías-Guiu and colleagues, twelve patients diagnosed with MS and 3 healthy controls underwent studies with MRI and [ 18 F]florbetaben-PET imaging.…”