Increased plasma amyloid-β42 protein in sporadic inclusion body myositis

Sporadic inclusion body myositis (s-IBM) is the most frequently acquired myopathy above the age of 50 years. Although the pathogenesis of s-IBM is largely unknown, an underlying myodegenerative process involving amyloid β protein (Aβ) accumulation has been proposed as a pathophysiological mechanism [1]. Here, we examined whether there are changes in the plasma levels of Aβ42 and Aβ40 in patients with s-IBM, patients with other inflammatory myopathies, and age-matched controls. All patients diagnosed with an inflammatory myopathy before January 2006 were retrieved from the Dutch neuromuscular database (CRAMP = Computer Registry of All Myopathies and Polyneuropathies) [4]. Of the 152 registered patients, 49 patients were excluded because they could not be traced (n = 11), were deceased (n = 26) or declined to participate (n = 12). We included 31 patients with s-IBM, 49 with polymyositis (PM) and 23 with dermatomyositis (DM). Thirty-four neurologically healthy spouses were selected as age-matched controls. Diagnosis of s-IBM, DM and PM was made according to established international criteria [3, 5]. Patients were visited at home. Functional status was scored using the modified Rankin-scores, and the Barthel index. Furthermore, total body weight, use of steroids or other immunosuppressive medication and statins (HMG-CoA reductase inhibitors) were noted. Local ethical committee approval, and written informed consent from all participants, was obtained. Plasma samples were aliquoted and frozen at −80°C until the time of analysis. Plasma concentrations of Aβ42 were measured by a commercial ELISA (Innotest β-amyloid(1–42) High Sensitivity Test; Innogenetics, Gent, Belgium). Aβ40 concentrations were measured by a commercially available assay based on the xMAP technology (Biosource, Camarillo, CA, USA) on a LiquiChip 100S analyzer (Qiagen, Venlo, The Netherlands). Comparisons of the plasma values between the groups were made using one-way ANOVA with Tukey post hoc test on logarithmically transformed data with covariate analysis of the baseline characteristics. Correlations between variables were calculated using Pearson’s correlation coefficient. SPSS version 14.0 was used to analyze the data. Baseline characteristics and plasma Aβ are shown in Tables 1 and ​and2.2. The median plasma Aβ42 levels were significantly increased in the s-IBM group versus controls and PM group. When we divided the s-IBM patients into two groups, with concentrations either above or below the median levels of Aβ42, we neither found any differences in demographic data nor in disease severity. Also, age or Rankin-scores or Barthel index, medication use, time interval from blood draw to spinning and freezing or other baseline characteristics did not correlate with Aβ42 or Aβ40 levels in the individual groups. Table 1 Patient characteristics Table 2 Mean plasma concentration of Aβ42 and Aβ40 This is the first study examining plasma levels of Aβ42 in patients with s-IBM compared to patients with other inflammatory myopathies and age-matched controls. Data of other studies hint to a degenerative contribution to the cause of s-IBM, where it was shown that intracellular amyloid deposits and Aβ immunoreactivity were found in affected muscle fibers of patients with s-IBM [1]. In addition, recent transgenic mice studies have shown that the deposition of Aβ may be a primary pathogenic mechanism in s-IBM [2]. This cross-sectional cohort study was designed for the sole purpose to test the hypothesis that the underlying neurodegenerative process in s-IBM could be reflected in altered Aβ plasma levels. Because of this design, plasma Aβ levels could not be correlated to the results of the muscle biopsies, because in many patients the diagnosis was made several years before we collected the plasma. Lack of matching in baseline characteristics (due to the intrinsic clinical characteristics of the included disorders) did not explain the differences in Aβ levels. Surprisingly, plasma Aβ levels were also increased in DM. A possible confounding factor could be that some of the DM patients could have developed IBM at time of this study, since there were older patients included in this group and the diagnosis was made previously, i.e., we did not perform new biopsies in patients that were diagnosed previously. Furthermore, kidney function can influence amyloid levels. Only one DM patient had a previous kidney problem in his medical history. The Aβ plasma concentrations of this patient were within the range of his group. However, specific laboratory data of kidney functions at time of the study were not available. The potential diagnostic value of plasma Aβ testing seems limited in our cross-sectional cohort because of the considerable overlap in concentrations. Further prospective investigations are required, to fully elucidate this and, in addition, to evaluate if plasma Aβ concentrations could be correlated to the severity or long-term outcome of this enigmatic disease.