CSF β-amyloid as a putative biomarker of disease progression in multiple sclerosis

Pietroboni, Anna M.; Cola, Francesca Schiano di; Scarioni, Marta; Fenoglio, Chiara; Spanò, Barbara; Arighi, Andrea; Cioffi, Sara; Oldoni, Emanuela; Riz, Milena A. De; Basilico, Paola; Calvi, Alberto; Fumagalli, Giorgio; Triulzi, Fabio; Galimberti, Daniela; Bozzali, Marco; Scarpini, Elio

doi:10.1177/1352458516674566

Cited by 37 publications

(38 citation statements)

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“…We recently described a relationship between low CSF Aβ levels and worse prognosis in MS [22,23]. In line with these findings and hypothesis [22], the correlation we describe between amyloid tracer uptake and CSF Aβ concentration suggests that amyloid plays a role in the progression of WM damage in MS. Thus, 18 F-florbetapir PET may represent a marker of early WM damage and a useful prognostic tool.…”

Section: Discussionsupporting

confidence: 87%

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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

Pietroboni

Carandini

Colombi

et al. 2018

Eur J Nucl Med Mol Imaging

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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.

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Section: Discussionsupporting

confidence: 87%

“…Reduced cerebrospinal fluid (CSF) Aβ levels have been reported in MS patients [18][19][20][21][22] and have recently been suggested as prognostic biomarker [22,23].…”

Section: Introductionmentioning

confidence: 99%

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

Pietroboni

Carandini

Colombi

et al. 2018

Eur J Nucl Med Mol Imaging

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“…Following our previous findings 12 , we recruited here a larger cohort of MS patients with a longer follow-up, classifying them as Aβ low and Aβ high based on their CSF Aβ levels. With respect to the clinical outcome, Aβ low showed a higher risk of disease progression.…”

Section: Discussionmentioning

confidence: 99%

“…A fraction of the population (n=48) has already been included in a previous study 12 . All patients underwent clinical assessment, brain MRI and lumbar puncture (LP).…”

Section: Subjectsmentioning

confidence: 99%

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CSF β-amyloid predicts prognosis in patients with multiple sclerosis

et al. 2018

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Background: The importance of predicting disease progression in multiple sclerosis (MS) has increasingly been recognised, hence reliable biomarkers are needed.Objectives: To investigate the prognostic role of cerebrospinal fluid (CSF) Amyloid beta1-42 (A) levels by the determination of a cut-off value to classify patients in slow and fast progressors. To evaluate possible association with white (WM) and grey matter (GM) damage at early disease stages.Methods: Sixty patients were recruited and followed-up for three to five years. Patients underwent clinical assessment, CSF analysis to determine Aβ levels, and brain MRI (at baseline and after 1 year). T1-weighted volumes were calculated. T2-weighted scans were used to quantify WM lesion loads.Results: Lower CSF Aβ levels were observed in patients with a worse follow-up EDSS (r=−0.65, p<0.001).The multiple regression analysis confirmed CSF Aβ concentration as a predictor of patients' EDSS increase (r=−0.59, p<0.0001). Generating a receiver operator characteristic curve, a cut-off value of 813 pg/ml was determined as the threshold able to identify patients with worse prognosis (95%CI 0.690-0.933, p=0.0001). No differences in CSF tau and NfL levels were observed (p>0.05).Conclusions: Low CSF Aβ levels may represent a predictive biomarker of disease progression in MS.

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Evidence of retinal anterograde neurodegeneration in the very early stages of multiple sclerosis: a longitudinal OCT study

et al. 2020

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CSF β-amyloid as a putative biomarker of disease progression in multiple sclerosis

Abstract: CSF Aβ reduction is a promising biomarker of neurodegeneration and may predict patients' clinical outcome. Therefore, CSF Aβ should be considered as a potential biomarker of prognostic value.

Cited by 37 publications

References 30 publications

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

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

CSF β-amyloid predicts prognosis in patients with multiple sclerosis

Evidence of retinal anterograde neurodegeneration in the very early stages of multiple sclerosis: a longitudinal OCT study

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