Skip to content
Universität Bonn
Universitätsklinikum Bonn

Aktuelle Publikationen

J Neurochem. 2020 Sep 7. doi: 10.1111/jnc.15175. Online ahead of print.

Affiliations

  • 1 German Center for Neurodegenerative Diseases (DZNE), Venusberg-Campus 1, 53127, Bonn, Germany.
  • 2 University of Bonn Medical Center, Department of Neurodegenerative Diseases & Geropsychiatry/Neurology, Venusberg, Campus 1, 53127, Bonn, Germany.
  • 3 University of Glasgow, 1263 Argylestreet, G3 8th, Glasgow, UK.
  • 4 University of Bonn Medical Center, Institute of Innate Immune, Venusberg-Campus 1, 53127, Bonn, Germany.
  • 5 Department of Psychiatry, University of Cologne, Medical Faculty, Kerpener Strasse 62, 50924, Cologne, Germany.

Abstract

There is growing evidence that promising biomarkers of inflammation in Alzheimer´s disease (AD) and other neurodegenerative diseases correlate strongest to levels of tau or neurofilament, indicating an inflammatory response to neuronal damage or death. To test this hypothesis, we investigated three AD candidate markers (ferritin, fatty acid binding protein 3 (FABP-3) and neurogranin) in interrelation to established AD and inflammatory protein markers. We further aimed to determine if such interrelations would be evident in pathological subjects only or also under non-pathological circumstances. Cerebrospinal fluid levels of the three proteins were quantified in samples from the University Clinic of Bonn (UKB) Department of Neurodegenerative Diseases & Geriatric Psychiatry, Germany. Data were analyzed based on clinical or biomarker-defined stratification of subjects with adjustment for covariates age, sex and APOE status. Levels of ferritin, FABP-3 and neurogranin were elevated in subjects with pathological levels of t-tau independent of beta-amyloid status. The three markers correlated to each other, tau isoforms, age, and those inflammatory markers previously described as related to neurodegeneration, predominantly sTREM2, MIF, sVEGF-R, sVCAM-1 and C1q. These interrelations existed in subjects with pathological and sub-pathological tau levels, in particular for FABP-3 and neurogranin. Relations to ferritin were independent of absolute levels of tau, too, but showed differing trajectories between pathological and non-pathological subjects. A specific set of inflammatory markers is highly related to markers of neuronal damage such as tau, neurogranin or FABP-3. These proteins could be used as readouts of the inflammatory response during the neurodegeneration phase of AD.

Alzheimers Res Ther. 2020 Jun 4;12(1):69. doi: 10.1186/s13195-020-00640-3.

Affiliations

  • 1 Department of Neurodegenerative Disease and Geriatric Psychiatry, University of Bonn, Bonn, Germany. Bitte aktivieren Sie JavaScript, um den verschlüsselten Inhalt zu sehen..
  • 2 German Center for Neurodegenerative Disease, Bonn, Germany. Bitte aktivieren Sie JavaScript, um den verschlüsselten Inhalt zu sehen..
  • 3 Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, 01605, USA. Bitte aktivieren Sie JavaScript, um den verschlüsselten Inhalt zu sehen..
  • 4 German Center for Neurodegenerative Disease, Bonn, Germany.
  • 5 Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
  • 6 Institute for Innate Immunity, University of Bonn, Bonn, Germany.
  • 7 Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, USA.
  • 8 Department of Neurology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.

Abstract

Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, less is known about the possible long-term consequences for the brain. Severely affected COVID-19 cases experience high levels of proinflammatory cytokines and acute respiratory dysfunction and often require assisted ventilation. All these factors have been suggested to cause cognitive decline. Pathogenetically, this may result from direct negative effects of the immune reaction, acceleration or aggravation of pre-existing cognitive deficits, or de novo induction of a neurodegenerative disease. This article summarizes the current understanding of neurological symptoms of COVID-19 and hypothesizes that affected patients may be at higher risk of developing cognitive decline after overcoming the primary COVID-19 infection. A structured prospective evaluation should analyze the likelihood, time course, and severity of cognitive impairment following the COVID-19 pandemic.

Keywords: Cognition; Cytokine; Decline; NLRP3 inflammasome; Neurodegeneration; Neuroinflammation; Systemic inflammation.

Affiliations

  • 1 German Center for Neurodegenerative Disease, Bonn, Germany.
  • 2 Department of Neurodegenerative Disease and Geriatric Psychiatry, University of Bonn Medical Center, Bonn, Germany.
  • 3 Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA.

    Abstract

    In this issue of JEM, Reed-Geaghan et al. (https://doi.org/10.1084/jem.20191374) address the long-standing question about the primary source of myeloid cells located at β-amyloid deposits. Using genetic labeling experiments, the authors identify resident microglia as the only myeloid cells present at β-amyloid deposits.

Lancet Neurol. 2020 Apr;19(4):285-287. doi: 10.1016/S1474-4422(20)30076-4. Epub 2020 Mar 18

Affiliations

  • 1 Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital of Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases, 53127 Bonn, Germany.
  • 2 Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital of Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases, 53127 Bonn, Germany; Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA. Electronic address: Bitte aktivieren Sie JavaScript, um den verschlüsselten Inhalt zu sehen..

Lea L Friker  1 Hannah Scheiblich  1 Inga V Hochheiser  2 Rebecca Brinkschulte  2 Dietmar Riedel  3 Eicke Latz  4 Matthias Geyer  2 Michael T Heneka  5

Cell Rep. 2020 Mar 17;30(11):3743-3754.e6. doi: 10.1016/j.celrep.2020.02.025.

1 Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology, University of Bonn Medical Center, 53127 Bonn, Germany.
2 Institute of Structural Biology, University of Bonn, 53127 Bonn, Germany.
3 Max Planck Institute for Biophysical Chemistry, Department of Structural Dynamics, 37077 Göttingen, Germany.
4 Institute of Innate Immunity, University of Bonn, 53127 Bonn, Germany.
5 Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology, University of Bonn Medical Center, 53127 Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany; Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: Bitte aktivieren Sie JavaScript, um den verschlüsselten Inhalt zu sehen..

Abstract

Alzheimer's disease is the world's most common neurodegenerative disorder. It is associated with neuroinflammation involving activation of microglia by β-amyloid (Aβ) deposits. Based on previous studies showing apoptosis-associated speck-like protein containing a CARD (ASC) binding and cross-seeding extracellular Aβ, we investigate the propagation of ASC between primary microglia and the effects of ASC-Aβ composites on microglial inflammasomes and function. Indeed, ASC released by a pyroptotic cell can be functionally built into the neighboring microglia NOD-like receptor protein (NLRP3) inflammasome. Compared with protein-only application, exposure to ASC-Aβ composites amplifies the proinflammatory response, resulting in pyroptotic cell death, setting free functional ASC and inducing a feedforward stimulating vicious cycle. Clustering around ASC fibrils also compromises clearance of Aβ by microglia. Together, these data enable a closer look at the turning point from acute to chronic Aβ-related neuroinflammation through formation of ASC-Aβ composites.

Keywords: ASC; Alzheimer’s disease; Aβ; NLRP3 inflammasome; microglia.

Information gemäß § 6 Medizinprodukte-Betreiberverordnung "Beauftragter für Medizinproduktesicherheit"

Sehr geehrte Damen und Herren,

gemäß § 6 Medizinprodukte-Betreiberverordnung steht Ihnen das Universitätsklinikum Bonn im Zusammenhang mit Meldungen über Risiken von Medizinprodukten, Informationen zu Rückrufen oder Warn- und Sicherheitshinweisen sowie bei der Umsetzung von notwendigen korrektiven Maßnahmen unter folgender E-Mailadresse zur Verfügung: Bitte aktivieren Sie JavaScript, um den verschlüsselten Inhalt zu sehen.

Diese E-Mailadresse richtet sich vorzugsweise an Kontaktpersonen von Behörden, Herstellern und Vertreibern von Medizinprodukten.