Objective: Elevated bone turnover observed in ALS patients suggests poor bone health and increased fracture risk. We therefore evaluated the relationship of fracture to subsequent ALS risk.
Methods: We followed 4,529,460 Swedes from 1987 to 2010 and identified ALS and fractures from the Swedish National Patient Register. We examined associations of ALS risk with all fractures, osteoporotic and non-osteoporotic fractures, and traumatic and non-traumatic fractures among individuals aged 30-80 years. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We analysed the association of ALS with time since fracture using a Poisson regression model.
Results: All fractures (HR: 1.51, 95% CI 1.39-1.65) as well as osteoporotic (HR: 1.59, 95% CI 1.41-1.79), non-osteoporotic (HR: 1.46, 95% CI 1.31-1.63), traumatic (HR: 1.50, 95% CI 1.37-1.63), and non-traumatic (HR: 1.80, 95% CI 1.35-2.40) fractures were associated with a higher incidence of ALS. Increased ALS incidence was associated with fractures occurring from one (HR: 2.33, 95% CI 2.04-2.66) to 18 (HR: 1.19, 95% CI 1.01-1.43) years before ALS diagnosis.
Conclusions: Poor bone health may be related to ALS. These findings may offer insight into ALS pathophysiology.
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http://dx.doi.org/10.1080/21678421.2017.1300287 | DOI Listing |
Neurol Clin Pract
April 2025
Department of Neurology, Emory University School of Medicine, Atlanta, GA.
Background And Objectives: Telemedicine has become a mainstay of ALS clinical care, but there is currently no standardized approach for assessing and tracking changes to the neurologic examination in this format. The goal of this study was to create a standardized telemedicine-based motor examination scale to objectively and reliably track ALS progression and use Rasch methodology to validate the scale and improve its psychometric properties.
Methods: A draft telemedicine examination scale with 25 items assessing movement in the bulbar muscles, neck, trunk, and extremities was created by an ALS expert panel, incorporating input from patient advisors.
Acta Naturae
January 2024
Research Center of neurology, Ministry of Science and Higher Education of the Russian Federation, Moscow, 125367 Russian Federation.
Amyotrophic lateral sclerosis (ALS) is a severe disease of the central nervous system (CNS) characterized by motor neuron damage leading to death from respiratory failure. The neurodegenerative process in ALS is characterized by an accumulation of aberrant proteins (TDP-43, SOD1, etc.) in CNS cells.
View Article and Find Full Text PDFCommun Chem
January 2025
Department of Chemistry, Indian Institute of Technology Delhi, New Delhi, India.
Superoxide dismutase 1 (SOD1) aggregation is implicated in the development of Amyotrophic Lateral Sclerosis (ALS). Despite knowledge of the role of SOD1 aggregation, the mechanistic understanding remains elusive. Our investigation aimed to unravel the complex steps involved in SOD1 aggregation associated with ALS.
View Article and Find Full Text PDFCommun Biol
January 2025
Université Paris-Saclay, INSERM U1204, Univ Evry, Structure-Activité des Biomolécules Normales et Pathologiques (SABNP), Evry-Courcouronnes, France.
Protein aggregation is a hallmark of many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), in which TDP-43, a nuclear RNA-binding protein, forms cytoplasmic inclusions. Here, we have developed a robust and automated method to assess protein self-assembly in the cytoplasm using microtubules as nanoplatforms. Importantly, we have analyzed specifically the self-assembly of full-length TDP-43 and its mRNA binding that are regulated by the phosphorylation of its self-adhesive C-terminus, which is the recipient of many pathological mutations.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Department of Agricultural Biotechnology, and Research Institute of Agriculture and Life Sciences, CALS, Seoul National University, Seoul 08826, Republic of Korea.
The formation of superoxide dismutase 1 (SOD1) filaments has been implicated in amyotrophic lateral sclerosis (ALS). Although the disulfide bond formed between Cys57 and Cys146 in the active state has been well studied, the role of the reduced cysteine residues, Cys6 and Cys111, in SOD1 filament formation remains unclear. In this study, we investigated the role of reduced cysteine residues by determining and comparing cryoelectron microscopy (cryo-EM) structures of wild-type (WT) and C6A/C111A SOD1 filaments under thiol-based reducing and metal-depriving conditions, starting with protein samples possessing enzymatic activity.
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