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Blood phosphorylated (p)-tau 181 and p-tau 217 have been proposed as accurate biomarkers of Alzheimer’s disease (AD) pathology. However, blood p-tau 181 is also elevated in amyotrophic lateral sclerosis (ALS) without a clearly identified source. We measured serum p-tau 181 and p-tau 217 in a multicentre cohort of ALS (n = 152), AD (n = 111) cases and disease controls (n = 99) recruited from four different centres. Further, we investigated the existence of both p-tau species using immunohistochemistry (IHC) and mass spectrometry (MS) in muscle biopsies of ALS cases (IHC: n = 13, MS: n = 5) and disease controls (IHC: n = 14, MS: n = 5) from one cohort. Serum p-tau 181 and p-tau 217 were higher in AD and ALS patients compared to disease controls. IHC and MS analyses revealed the presence of p-tau 181 and 217 in muscle biopsies from both ALS cases and disease controls, with ALS samples showing increased p-tau reactivity in atrophic muscle fibres. Blood p-tau species could potentially be used to diagnose both ALS and AD. Blood phosphorylated (p)-tau 181 and p-tau 217 have been proposed as accurate biomarkers of Alzheimer’s disease pathology. Here, the authors find p-tau 181 and 217 are elevated in serum and muscle of patients with amyotrophic lateral sclerosis.

Background Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by progressive muscle weakness due to SMN protein deficiency. While effective therapies exist, their impact on slowly progressive adult SMA patients remains unclear. Reliable biomarkers for monitoring disease progression and treatment response are urgently needed. This pilot study evaluated the utility of longitudinal quantitative muscle MRI (qMRI) to monitor disease progression in adult SMA patients treated with nusinersen over an extended period. Methods Nine adult patients with genetically confirmed 5q‐SMA underwent whole‐body muscle MRI and clinical assessment, including the Hammersmith Functional Motor Scale‐Expanded (HFMS‐EXP), Revised Upper Limb Module (RULM), and 6 min walk test (6MWT). Muscular fat fraction (mFF) was quantified in 20 muscles over a median follow‐up of 54 months. Results Baseline mFF correlated strongly with clinical measures (HFMS‐EXP: r = −0.90, p = 0.001; 6MWT: r = −0.96, p < 0.001), but not with age at onset or age at MRI. Over the observation period, a significant increase in mFF was detected (averaged annual increase of all studied muscles: 0.47%, p = 0.011), accentuated in the lower leg muscles. In contrast, clinical measures showed no consistent change. Consequently, no significant correlations were found between changes in mFF and clinical scores. Conclusions This study provides the longest reported longitudinal qMRI assessment in adult SMA patients treated with nusinersen, demonstrating that mFF progressively increases despite stable clinical scores. The results suggest that qMRI may be a sensitive and objective biomarker for detecting subtle disease progression in adult SMA, potentially surpassing clinical measures. Quantitative muscle MRI is emerging as an objective biomarker for monitoring therapy in neuromuscular disorders, yet long‐term trajectories in slowly progressive adult spinal muscular atrophy (SMA) remain unclear. In this study, quantitative MRI parameters in nusinersen‐treated adults were longitudinally evaluated and compared with established clinical outcome measures. MRI detected progression with higher sensitivity than conventional measures, supporting its use as an objective addition to the SMA monitoring toolbox and motivating validation in larger cohorts.

In recent years, the use of carbon fibers (CFs) in various sectors of industry has been increasing. Despite the similarity of CF degradation products to other toxicologically relevant materials such as asbestos fibers and carbon nanotubes, a detailed toxicological evaluation of this class of material has yet to be performed. In this work, we exposed advanced air–liquid interface cell culture models of the human lung to CF. To simulate different stresses applied to CF throughout their life cycle, they were either mechanically (mCF) or thermo-mechanically pre-treated (tmCF). Different aspects of inhalation toxicity as well as their possible time-dependency were monitored. mCFs were found to induce a moderate inflammatory response, whereas tmCF elicited stronger inflammatory as well as apoptotic effects. Furthermore, thermal treatment changed the surface properties of the CF resulting in a presumed adhesion of the cells to the fiber fragments and subsequent cell loss. Triple-cultures encompassing epithelial, macrophage, and fibroblast cells stood out with an exceptionally high inflammatory response. Only a weak genotoxic effect was detected in the form of DNA strand breaks in mono- and co-cultures, with triple-cultures presenting a possible secondary genotoxicity. This work establishes CF fragments as a potentially harmful material and emphasizes the necessity of further toxicological assessment of existing and upcoming advanced CF-containing materials.