Low CSF β-amyloid levels predict early regional grey matter atrophy in multiple sclerosis

Abstract Background and purpose : Grey matter (GM) atrophy is present from the earliest stages of multiple sclerosis (MS) and occurs largely in a nonrandom manner. However, the biological mechanisms underlying the progression of regional atrophy are still unclear. Aim of this study is to investigate whether amyloid pathology might be involved in determining the pattern of GM atrophy over time. Methods : Forty-six subjects were recruited: 31 newly diagnosed relapsing-remitting (RR-) MS patients and 15 age- and sex-matched healthy controls (HC). Aβ levels were determined in CSF samples from all subjects. All participants underwent brain magnetic resonance imaging (MRI) at baseline, and 23 out of 31 patients at one year follow-up. T1-weighted scans were segmented using the Geodesic Information Flows software. Non-parametric statistical tests were used for between-group comparisons and multiple regression analyses. Results : CSF Aβ concentration was the best predictor of global GM loss over time after age (β=0.403; p=0.024), in particular in the left precuneus (p=0.045), in the left middle cingulate gyrus (p=0.009), in the left precentral gyrus (p=0.021) and in the right angular gyrus (p=0.029). Conclusions : CSF Aβ levels seem to be crucial in MS early brain volume loss as GM atrophy manifests in regions particularly vulnerable to early Aβ deposition.