CSF β-amyloid predicts prognosis in patients with multiple sclerosis

Abstract

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.

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

“…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.…”

“…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].…”

Amyloid‐β immunotherapy for alzheimer disease: Is it now a long shot?

“…Interestingly, brain Aβ may be increased in numerous neurologic conditions other than AD: traumatic brain injury, chronic traumatic encephalopathy, general anesthesia, amyotrophic lateral sclerosis, major depressive disorder, cerebral ischemia, and multiple sclerosis . Patients undergoing cardiac surgery or suffering cardiac arrest also show rapid changes in Aβ levels in CSF/plasma, even infants and children, probably from a combination of mechanical trauma and anesthetic insult.…”

Cerebrospinal fluid A beta 1–40 peptides increase in Alzheimer’s disease and are highly correlated with phospho-tau in control individuals

“…This ratio can also be used to account for inter-individual amyloid variations in the baseline CSF level [ 28 ]. Low CSF Aβ40 levels might also be indicative of frontotemporal dementia (FTD) [ 29 , 30 ], cerebral amyloid angiopathy (CAA) [ 31 ], HIV [ 32 ], multiple sclerosis [ 33 ], or normal pressure hydrocephalus (NPH) [ 34 ].…”