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  1. Article ; Online: Cystatin C based estimation of chronic kidney disease and amyotrophic lateral sclerosis in the ALS registry Swabia: associated risk and prognostic value.

    Nagel, Gabriele / Kurz, Deborah / Peter, Raphael S / Rosenbohm, Angela / Koenig, Wolfgang / Dupuis, Luc / Bäzner, Hansjörg / Börtlein, Axel / Dempewolf, Silke / Schabet, Martin / Hecht, Martin / Kohler, Andreas / Opherk, Christian / Naegele, Andrea / Sommer, Norbert / Lindner, Alfred / Tumani, Hayrettin / Ludolph, Albert C / Rothenbacher, Dietrich

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 19594

    Abstract: ... on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation, and the risk at onset and prognostic ... months), 317 died. Serum samples were measured for cystatin C to estimate the glomerular filtration rate ... cystatin-C based eGFR concentrations were lower in ALS cases than in controls (54.0 vs. 59.5 mL/min pro 1 ...

    Abstract Kidney function as part of metabolic changes could be associated with amyotrophic lateral-sclerosis (ALS). We investigated the associations between estimated chronic kidney disease (CKD), based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation, and the risk at onset and prognostic value of CKD for ALS. Between October 2010 and June 2014, 362 ALS cases (59.4% men, mean age 65.7 years) and 681 controls (59.5% men, means age 66.3 years) were included in a population-based case-control study based on the ALS registry Swabia in Southern Germany. All ALS cases were followed-up (median 89.7 months), 317 died. Serum samples were measured for cystatin C to estimate the glomerular filtration rate (eGFR) according to the CKD-EPI equation. Information on covariates were assessed by an interview-based standardized questionnaire. Conditional logistic regression models were applied to calculate odds ratios (OR) for risk of ALS associated with eGFR/CKD stages. Time-to-death associated with renal parameters at baseline was assessed in ALS cases only. ALS cases were characterized by lower body mass index, slightly lower smoking prevalence, more intense occupational work and lower education than controls. Median serum cystatin-C based eGFR concentrations were lower in ALS cases than in controls (54.0 vs. 59.5 mL/min pro 1.73 m
    MeSH term(s) Male ; Humans ; Aged ; Female ; Prognosis ; Amyotrophic Lateral Sclerosis ; Case-Control Studies ; Prospective Studies ; Cystatin C ; Renal Insufficiency, Chronic/complications ; Glomerular Filtration Rate ; Registries ; Creatinine ; Biomarkers
    Chemical Substances Cystatin C ; Creatinine (AYI8EX34EU) ; Biomarkers
    Language English
    Publishing date 2023-11-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-46179-9
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  2. Article ; Conference proceedings: Tau PET/CT mit C-11-PBB3 in Patienten mit Verdacht auf eine neurodegenerative Erkrankung vom Typ AD oder FTLD in der klinischen Routine: Korrelation von PET-Bildgebung und CSF Biomarkern

    Strobel, J. / Yousefzadeh-Nowshahr, E. / Deininger, K. / Bohn, K. P. / von Arnim, C. / Otto, M. / Solbach, C. / Anderl-Straub, S. / Polivka, D. / Fissler, P. / Glatting, G. / Riepe, M. W. / Higuchi, M. / Beer, A. J. / Ludolph, A. / Winter, G.

    Nuklearmedizin - NuclearMedicine

    2024  Volume 63, Issue 02

    Event/congress 62. Jahrestagung der Deutschen Gesellschaft für Nuklearmedizin, Leipzig, 2024-04-10
    Language German
    Publishing date 2024-03-01
    Publisher Georg Thieme Verlag
    Publishing place Stuttgart ; New York
    Document type Article ; Conference proceedings
    ZDB-ID 2030804-8
    ISSN 2567-6407 ; 0029-5566
    ISSN (online) 2567-6407
    ISSN 0029-5566
    DOI 10.1055/s-0044-1782451
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  3. Article: The m.9143T>C Variant: Recurrent Infections and Immunodeficiency as an Extension of the Phenotypic Spectrum in

    Urban, Diana Lehmann / Scholle, Leila Motlagh / Wagner, Matias / Ludolph, Albert C / Rosenbohm, Angela

    Diseases (Basel, Switzerland)

    2020  Volume 8, Issue 2

    Abstract: Pathogenic variants in ... ...

    Abstract Pathogenic variants in the
    Language English
    Publishing date 2020-06-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720869-2
    ISSN 2079-9721
    ISSN 2079-9721
    DOI 10.3390/diseases8020019
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  4. Article ; Online: The m.9143T>C Variant

    Diana Lehmann Urban / Leila Motlagh Scholle / Matias Wagner / Albert C. Ludolph / Angela Rosenbohm

    Diseases, Vol 8, Iss 19, p

    Recurrent Infections and Immunodeficiency as an Extension of the Phenotypic Spectrum in MT-ATP6 Mutations?

    2020  Volume 19

    Abstract: ... Single-exome sequencing revealed a variant in the MT-ATP6 gene: m.9143T>C. Analysis of further specimen ...

    Abstract Pathogenic variants in the MT-ATP6 are a well-known cause for maternally inherited mitochondrial disorders associated with a wide range of clinical phenotypes. Here, we present a 31- year old female with insulin-dependent diabetes mellitus, recurrent lactic acidosis and ketoacidosis recurrent infections with suspected immunodeficiency with T cell lymphopenia and hypogammaglobulinemia as well as proximal tetraparesis with severe muscle and limb pain and rapid physical exhaustion. Muscle biopsy and respiratory chain activities were normal. Single-exome sequencing revealed a variant in the MT-ATP6 gene: m.9143T>C. Analysis of further specimen of the index and mother (segregation studies) revealed the highest mutation load in muscle (99% level of mtDNA heteroplasmy) of the index patient. Interestingly, acute metabolic and physical decompensation during recurrent illness was documented to be a common clinical feature in patients with MT-ATP6 variants. However, it was not mentioned as a key symptom. Thus, we suggest that the clinical spectrum might be expanded in ATP6 -associated diseases.
    Keywords MT-ATP6 ; mitochondrial disease ; immune deficiency ; phenotypic spectrum ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Correction to: Integrative proteomics highlight presynaptic alterations and c-Jun misactivation as convergent pathomechanisms in ALS.

    Aly, Amr / Laszlo, Zsofia I / Rajkumar, Sandeep / Demir, Tugba / Hindley, Nicole / Lamont, Douglas J / Lehmann, Johannes / Seidel, Mira / Sommer, Daniel / Franz-Wachtel, Mirita / Barletta, Francesca / Heumos, Simon / Czemmel, Stefan / Kabashi, Edor / Ludolph, Albert / Boeckers, Tobias M / Henstridge, Christopher M / Catanese, Alberto

    Acta neuropathologica

    2023  Volume 146, Issue 5, Page(s) 783

    Language English
    Publishing date 2023-09-12
    Publishing country Germany
    Document type Published Erratum
    ZDB-ID 1079-0
    ISSN 1432-0533 ; 0001-6322
    ISSN (online) 1432-0533
    ISSN 0001-6322
    DOI 10.1007/s00401-023-02630-9
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    In stock of ZB MED Cologne/Königswinter

    Ui II Zs.188: Show issues Location:
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  6. Article ; Online: Integrative proteomics highlight presynaptic alterations and c-Jun misactivation as convergent pathomechanisms in ALS.

    Aly, Amr / Laszlo, Zsofia I / Rajkumar, Sandeep / Demir, Tugba / Hindley, Nicole / Lamont, Douglas J / Lehmann, Johannes / Seidel, Mira / Sommer, Daniel / Franz-Wachtel, Mirita / Barletta, Francesca / Heumos, Simon / Czemmel, Stefan / Kabashi, Edor / Ludolph, Albert / Boeckers, Tobias M / Henstridge, Christopher M / Catanese, Alberto

    Acta neuropathologica

    2023  Volume 146, Issue 3, Page(s) 451–475

    Abstract: ... to an accumulation of cytotoxic protein aggregates and to the pro-apoptotic activation of the transcription factor c ...

    Abstract Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease mainly affecting upper and lower motoneurons. Several functionally heterogeneous genes have been associated with the familial form of this disorder (fALS), depicting an extremely complex pathogenic landscape. This heterogeneity has limited the identification of an effective therapy, and this bleak prognosis will only improve with a greater understanding of convergent disease mechanisms. Recent evidence from human post-mortem material and diverse model systems has highlighted the synapse as a crucial structure actively involved in disease progression, suggesting that synaptic aberrations might represent a shared pathological feature across the ALS spectrum. To test this hypothesis, we performed the first comprehensive analysis of the synaptic proteome from post-mortem spinal cord and human iPSC-derived motoneurons carrying mutations in the major ALS genes. This integrated approach highlighted perturbations in the molecular machinery controlling vesicle release as a shared pathomechanism in ALS. Mechanistically, phosphoproteomic analysis linked the presynaptic vesicular phenotype to an accumulation of cytotoxic protein aggregates and to the pro-apoptotic activation of the transcription factor c-Jun, providing detailed insights into the shared pathobiochemistry in ALS. Notably, sub-chronic treatment of our iPSC-derived motoneurons with the fatty acid docosahexaenoic acid exerted a neuroprotective effect by efficiently rescuing the alterations revealed by our multidisciplinary approach. Together, this study provides strong evidence for the central and convergent role played by the synaptic microenvironment within the ALS spinal cord and highlights a potential therapeutic target that counteracts degeneration in a heterogeneous cohort of human motoneuron cultures.
    MeSH term(s) Humans ; Amyotrophic Lateral Sclerosis/pathology ; Neurodegenerative Diseases/pathology ; Proteomics ; Superoxide Dismutase-1/genetics ; Motor Neurons/metabolism
    Chemical Substances Superoxide Dismutase-1 (EC 1.15.1.1)
    Language English
    Publishing date 2023-07-24
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1079-0
    ISSN 1432-0533 ; 0001-6322
    ISSN (online) 1432-0533
    ISSN 0001-6322
    DOI 10.1007/s00401-023-02611-y
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    In stock of ZB MED Cologne/Königswinter

    Ui II Zs.188: Show issues Location:
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  7. Article ; Conference proceedings: Regional tau deposition in probable Alzheimer’s disease using C-11-PBB3-PET: a voxel-wise statistical analysis

    Yousefzadeh-Nowshahr, E / Winter, G / Bohn, K / Kneer, K / von Arnim, C / Otto, M / Solbach, C / Anderl-Straub, S / Polivka, D / Fissler, P / Prasad, V / Kletting, P / Riepe, M / Higuchi, M / Ludolph, A / Beer, AJ / Glatting, G

    Nuklearmedizin - NuclearMedicine

    2020  Volume 59, Issue 02

    Event/congress NuklearMedizin 2020, Leipzig, 2020-07-06
    Language German
    Publishing date 2020-04-01
    Publisher © Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article ; Conference proceedings
    ZDB-ID 2030804-8
    ISSN 2567-6407 ; 0029-5566
    ISSN (online) 2567-6407
    ISSN 0029-5566
    DOI 10.1055/s-0040-1708399
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  8. Article ; Online: Cystatin C based estimation of chronic kidney disease and amyotrophic lateral sclerosis in the ALS registry Swabia

    Gabriele Nagel / Deborah Kurz / Raphael S. Peter / Angela Rosenbohm / Wolfgang Koenig / Luc Dupuis / Hansjörg Bäzner / Axel Börtlein / Silke Dempewolf / Martin Schabet / Martin Hecht / Andreas Kohler / Christian Opherk / Andrea Naegele / Norbert Sommer / Alfred Lindner / Hayrettin Tumani / Albert C. Ludolph / Dietrich Rothenbacher

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    associated risk and prognostic value

    2023  Volume 8

    Abstract: ... on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation, and the risk at onset and prognostic ... months), 317 died. Serum samples were measured for cystatin C to estimate the glomerular filtration rate ... cystatin-C based eGFR concentrations were lower in ALS cases than in controls (54.0 vs. 59.5 mL/min pro 1 ...

    Abstract Abstract Kidney function as part of metabolic changes could be associated with amyotrophic lateral-sclerosis (ALS). We investigated the associations between estimated chronic kidney disease (CKD), based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation, and the risk at onset and prognostic value of CKD for ALS. Between October 2010 and June 2014, 362 ALS cases (59.4% men, mean age 65.7 years) and 681 controls (59.5% men, means age 66.3 years) were included in a population-based case–control study based on the ALS registry Swabia in Southern Germany. All ALS cases were followed-up (median 89.7 months), 317 died. Serum samples were measured for cystatin C to estimate the glomerular filtration rate (eGFR) according to the CKD-EPI equation. Information on covariates were assessed by an interview-based standardized questionnaire. Conditional logistic regression models were applied to calculate odds ratios (OR) for risk of ALS associated with eGFR/CKD stages. Time-to-death associated with renal parameters at baseline was assessed in ALS cases only. ALS cases were characterized by lower body mass index, slightly lower smoking prevalence, more intense occupational work and lower education than controls. Median serum cystatin-C based eGFR concentrations were lower in ALS cases than in controls (54.0 vs. 59.5 mL/min pro 1.73 m2). The prevalence of CKD stage ≥ 3 was slightly higher in ALS cases than in controls (14.1 vs. 11.0%). In the adjusted models, CKD stage 2 (OR 1.82, 95% CI 1.32, 2.52) and stage 3 (OR 2.34, 95% CI 1.38, 3.96) were associated with increased ALS risk. In this cohort of ALS cases, eGFR and CKD stage ≥ 3 (HR 0.94; 95% CI 0.64, 1.38) were not associated with prognosis. In this case–control study, higher CKD stages were associated with increased ALS risk, while in the prospective cohort of ALS cases, no indication of an association of CysC-based CKD on mortality was seen. In addition, our work strengthens the importance to evaluate renal function using a marker ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Adipokines, C-reactive protein and Amyotrophic Lateral Sclerosis - results from a population- based ALS registry in Germany.

    Nagel, Gabriele / Peter, Raphael S / Rosenbohm, Angela / Koenig, Wolfgang / Dupuis, Luc / Rothenbacher, Dietrich / Ludolph, Albert C

    Scientific reports

    2017  Volume 7, Issue 1, Page(s) 4374

    Abstract: To investigate the associations of leptin, adiponectin and high-sensitive (hs) C-reactive protein ...

    Abstract To investigate the associations of leptin, adiponectin and high-sensitive (hs) C-reactive protein (CRP) with risk and prognosis of amyotrophic lateral sclerosis (ALS). Data from a population-based case-control study in Southern Germany (10/2010-6/2014) of 289 ALS patients (mean age of 65.7 (SD 10.5) years, 59.5% men) and 506 controls were included. During median follow-up of 14.5 months of 279 ALS patients 104 (53.9% men, 68.9 (10.3) years) died. Serum samples were measured for leptin, adiponectin and hs-CRP. Conditional logistic regression was used to estimate ALS risk. Survival models were used to appraise the prognostic value. ALS patients were characterized by lower levels of school education, BMI and smoking prevalence. Adjusted for covariates, leptin was inversely associated with ALS risk (top vs. bottom quartile: OR 0.49; 95% CI 0.29-0.80), while for adiponectin a positive association was found (OR 2.89; 95% CI 1.78-4.68). Among ALS patients increasing leptin concentrations were associated with longer survival (p for trend 0.002), while for adiponectin no association was found (p for trend 0.55). For hs-CRP no association was found. Leptin and adiponectin, two key hormones regulating energy metabolism, were strongly and independently related with ALS risk. Leptin levels were further negatively related with overall survival of ALS patients.
    MeSH term(s) Adipokines/metabolism ; Aged ; Amyotrophic Lateral Sclerosis/epidemiology ; Amyotrophic Lateral Sclerosis/etiology ; Amyotrophic Lateral Sclerosis/metabolism ; Amyotrophic Lateral Sclerosis/mortality ; Biomarkers ; C-Reactive Protein/metabolism ; Disease Susceptibility ; Female ; Follow-Up Studies ; Germany/epidemiology ; Humans ; Male ; Middle Aged ; Odds Ratio ; Population Surveillance ; Registries ; Survival Analysis
    Chemical Substances Adipokines ; Biomarkers ; C-Reactive Protein (9007-41-4)
    Language English
    Publishing date 2017-06-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-017-04706-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Conference proceedings: Tau PET/CT Bildgebung mit C-11-PBB3 in Patienten mit Verdacht auf neurodegenerative Erkrankungen des AD- und FTLD-Spektrums

    Winter, G / Bohn, KP / Arnim, C von / Otto, M / Solbach, C / Glatting, G / Prasad, V / Polivka, D / Straub, S / Riepe, MW / Braak, H / Del Tredici, K / Higuchi, M / Ludolph, A / Beer, AJ

    Nuklearmedizin

    2019  Volume 58, Issue 02

    Event/congress NuklearMedizin 2019, Bremen, 2019-04-03
    Language German
    Publishing date 2019-03-01
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article ; Conference proceedings
    ZDB-ID 2030804-8
    ISSN 2567-6407 ; 0029-5566
    ISSN (online) 2567-6407
    ISSN 0029-5566
    DOI 10.1055/s-0039-1683663
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