5,349 results match your criteria: "German Center for Neurodegenerative Diseases DZNE[Affiliation]"

Article Synopsis
  • Human prion diseases are unusual brain illnesses that can spread and cause quick changes in memory and thinking.
  • The study looked at a specific type called sporadic Creutzfeldt-Jakob disease (sCJD), examining data from over 3,700 cases to understand how long the disease lasts and at what age it starts.
  • Researchers found important genetic clues on chromosome 20 that can help understand how long people live with this disease, especially one specific genetic change that seems to have a big effect on survival time.
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Background: The Target Product Profile (TPP) is a tool used in industry to guide development strategies by addressing user needs and fostering effective communication among stakeholders. However, they are not frequently used in academic research, where they may be equally useful. This systematic review aims to extract the features of accessible TPPs, to identify commonalities and facilitate their integration in academic research methodology.

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Artificial T1-Weighted Postcontrast Brain MRI: A Deep Learning Method for Contrast Signal Extraction.

Invest Radiol

February 2025

From the Clinic of Neuroradiology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany (R.H., E.K., Z.B., C.G., D.P., A.R., K.D.); Institute of Applied Mathematics, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany (T.P., A.E.); Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.P.); and German Center for Neurodegenerative Diseases (DZNE), Helmholtz Association of German Research Centers, Bonn, Germany (A.R., K.D.).

Article Synopsis
  • The study aimed to compare three methods for synthesizing full-dose T1-weighted MRI images to reduce the use of gadolinium-based contrast agents, focusing on safety, cost, and environmental impact.
  • A group of 213 participants underwent MRI scans using both low-dose and full-dose gadolinium, with the performance of the methods evaluated through a reader-based analysis.
  • Results indicated that the proposed method (setting C) outperformed the other two methods (A and B) in terms of interchangeability and lesion enhancement conformity, showing fewer false positives and a lower mean reduction in enhancement compared to true images.
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Article Synopsis
  • The study explores the genetic risk factors for Alzheimer's disease (AD) and their connection to various brain changes, aiming to enhance precision medicine strategies.
  • Researchers calculated specific genetic risk scores in healthy individuals to see how these scores correlate with AD-related biomarkers found in cerebrospinal fluid and imaging techniques.
  • Findings show that different genetic pathways link to distinct brain conditions, such as inflammation affecting vascular health and other pathways influencing white matter and brain connectivity, highlighting the complexity of AD and its potential for personalized treatment approaches.
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Introduction: Subjective cognitive decline (SCD) in amyloid-positive (Aβ+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies.

Methods: Eight hundred twenty-one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers.

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Neuronal communication relies on precisely maintained synaptic vesicle (SV) clusters, which assemble via liquid-liquid phase separation (LLPS). This process requires synapsins, the major synaptic phosphoproteins, which are known to bind actin. The reorganization of SVs, synapsins and actin is a hallmark of synaptic activity, but their interplay is still unclear.

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Towards multicenter β-amyloid PET imaging in mouse models: A triple scanner head-to-head comparison.

Neuroimage

August 2024

Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany; Center of Neuropathology and Prion Research, University of Munich, Munich Germany. Electronic address:

Aim: β-amyloid (Aβ) small animal PET facilitates quantification of fibrillar amyloidosis in Alzheimer's disease (AD) mouse models. Thus, the methodology is receiving growing interest as a monitoring tool in preclinical drug trials. In this regard, harmonization of data from different scanners at multiple sites would allow the establishment large collaborative cohorts and may facilitate efficacy comparison of different treatments.

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Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. A total of 25 healthy adults (25.

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Article Synopsis
  • The study aimed to create a shorter version of the Progressive Supranuclear Palsy quality of life scale (PSP-QoL) to make it easier for patients, especially those with cognitive impairments, to complete.
  • Involved a retrospective analysis of data from 245 PSP patients in Germany, resulting in a condensed 12-item scale that covers mental and physical aspects of daily living.
  • The new scale, called the PSP-ShoQoL, showed strong correlations with existing measures of quality of life and demonstrated its sensitivity to changes over time.
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Article Synopsis
  • Clinical trials for spinocerebellar ataxias (SCA) need better endpoints to measure early disease progression and effectiveness of treatments, as current measures focus on later stages.
  • The READISCA consortium found that advanced multimodal magnetic resonance imaging (MRI) can track changes in brain structure and function over 6 months in participants with early-stage SCA mutations, indicating disease progression.
  • Results showed significant differences in microstructural changes between SCA patients and controls, suggesting that diffusion MRI could reduce the sample size needed for future trials compared to traditional assessments like the Scale for Assessment and Rating of Ataxia (SARA).
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Purpose: T -weighted turbo-spin-echo (TSE) sequences are a fundamental technique in brain imaging but suffer from field inhomogeneities at ultra-high fields. Several methods have been proposed to mitigate the problem, but were limited so far to nonselective three-dimensional (3D) measurements, making short acquisitions difficult to achieve when targeting very high resolution images, or needed additional calibration procedures, thus complicating their application.

Methods: Slab-selective excitation pulses were designed for flexible placement utilizing the concept of k -spokes.

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Article Synopsis
  • The introduction of the antisense oligonucleotide tofersen for treating ALS caused by SOD1 mutations emphasizes the need to clarify the impact of over 230 SOD1 variants, particularly the debated p.D91A variant common in Europe.
  • A study involving 11 ALS patients treated with tofersen for up to 16 months shows that it significantly reduces serum neurofilament light chain (sNfL) levels, which are linked to ALS progression, in both homozygous and heterozygous SOD1 patients.
  • These findings support the role of mono- and bi-allelic SOD1 variants as relevant targets for treatment, offering a new perspective for assessing causality based on biomarker responses in clinical
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AAontology: An Ontology of Amino Acid Scales for Interpretable Machine Learning.

J Mol Biol

October 2024

Department of Bioinformatics, School of Life Sciences, Technical University of Munich, Freising, Germany. Electronic address:

Amino acid scales are crucial for protein prediction tasks, many of them being curated in the AAindex database. Despite various clustering attempts to organize them and to better understand their relationships, these approaches lack the fine-grained classification necessary for satisfactory interpretability in many protein prediction problems. To address this issue, we developed AAontology-a two-level classification for 586 amino acid scales (mainly from AAindex) together with an in-depth analysis of their relations-using bag-of-word-based classification, clustering, and manual refinement over multiple iterations.

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Social play behavior is driven by glycine-dependent mechanisms.

Curr Biol

August 2024

Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Neuroscience Research Center, 10117 Berlin, Germany; Humboldt-Universität zu Berlin, Bernstein Center for Computational Neuroscience, Philippstr. 13, 10115 Berlin, Germany; Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, NeuroCure Cluster of Excellence, 10117 Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE), 10117 Berlin, Germany; Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Einstein Center for Neuroscience, 10117 Berlin, Germany; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, 13125 Berlin, Germany. Electronic address:

Social play is pervasive in juvenile mammals, yet it is poorly understood in terms of its underlying brain mechanisms. Specifically, we do not know why young animals are most playful and why most adults cease to social play. Here, we analyze the synaptic mechanisms underlying social play.

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Innate immune training restores pro-reparative myeloid functions to promote remyelination in the aged central nervous system.

Immunity

September 2024

Institute of Neuronal Cell Biology, Technical University Munich, 81377 Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; Munich Cluster of Systems Neurology (SyNergy), 81377 Munich, Germany; Institute for Stroke and Dementia Research, University Hospital of Munich, LMU Munich, 81377 Munich, Germany. Electronic address:

The reduced ability of the central nervous system to regenerate with increasing age limits functional recovery following demyelinating injury. Previous work has shown that myelin debris can overwhelm the metabolic capacity of microglia, thereby impeding tissue regeneration in aging, but the underlying mechanisms are unknown. In a model of demyelination, we found that a substantial number of genes that were not effectively activated in aged myeloid cells displayed epigenetic modifications associated with restricted chromatin accessibility.

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A neuron's suitability to participate in a memory trace is modulated by its epigenetic state.

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Autoantibodies against proteins in the brain are increasingly considered as a potential cause of cognitive decline, not only in subacute autoimmune encephalopathies but also in slowly progressing impairment of memory in patients with classical neurodegenerative dementias. In this retrospective cohort study of 161 well-characterized patients with different forms of dementia and 34 controls, we determined the prevalence of immunoglobulin (Ig) G and IgA autoantibodies to brain proteins using unbiased immunofluorescence staining of unfixed murine brain sections. Autoantibodies were detected in 21.

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Six-month follow-up of multidomain cognitive impairment in non-hospitalized individuals with post-COVID-19 syndrome.

Eur Arch Psychiatry Clin Neurosci

December 2024

Department of Psychiatry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Some people infected with SARS-CoV-2 report persisting symptoms following acute infection. If these persist for over three months, they are classified as post-COVID-19 syndrome (PCS). Although PCS is frequently reported, detailed longitudinal neuropsychological characterization remains scarce.

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Introduction: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD.

Methods: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD.

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Previous studies have often reported timing deficits in older adults with different degrees of cognitive decline, however, the exact nature of impairments in time perception is still to be elucidated. In particular, it is unclear if the deficits are more pronounced for short or long intervals, consistent with notions that different cognitive processes and neuroanatomical areas are involved in the processing of durations of different ranges. The present study aims to further investigate timing abilities in amnestic mild cognitive impairment (aMCI) patients and age-matched controls.

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Innate immune memory after brain injury drives inflammatory cardiac dysfunction.

Cell

August 2024

Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. Electronic address:

Article Synopsis
  • - Chronic comorbidities following a stroke contribute significantly to patient health, and this study investigates how immune system changes may play a role in these issues.
  • - Researchers discovered that the immune response, particularly in monocytes/macrophages, remains persistently pro-inflammatory in various organs, especially the heart, even months after a stroke.
  • - Targeting IL-1β and blocking certain immune cell movement successfully prevented heart dysfunction in a study, suggesting potential new therapies for managing post-stroke complications.
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Genetically encoded calcium indicators (GECIs) such as GCaMP are invaluable tools in neuroscience to monitor neuronal activity using optical imaging. The viral transduction of GECIs is commonly used to target expression to specific brain regions, can be conveniently used with any mouse strain of interest without the need for prior crossing with a GECI mouse line, and avoids potential hazards due to the chronic expression of GECIs during development. A key requirement for monitoring neuronal activity with an indicator is that the indicator itself minimally affects activity.

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Multidisciplinary care in Parkinson's disease.

J Neural Transm (Vienna)

October 2024

Department of Neurology, Asklepios Klinik Barmbek, Hamburg, Germany.

Parkinson's Disease (PD) is a multifaceted and progressive disorder characterized by a diverse range of motor and non-motor symptoms. The complexity of PD necessitates a multidisciplinary approach to manage both motor symptoms, such as bradykinesia, gait disturbances and falls, and non-motor symptoms, including cognitive dysfunction, sleep disturbances, and mood disorders, which significantly affect patients' quality of life. Pharmacotherapy, particularly dopaminergic replacement therapy, has advanced to alleviate many symptoms.

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The CSF1R gene, located on chromosome 5, encodes a 108 kDa protein and plays a critical role in regulating myeloid cell function. Mutations in CSF1R have been identified as a cause of a rare white matter disease called adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP, also known as CSF1R-related leukoencephalopathy), characterized by progressive neurological dysfunction. This study aimed to broaden the genetic basis of ALSP by identifying novel CSF1R variants in patients with characteristic clinical and imaging features of ALSP.

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Article Synopsis
  • Many studies on brain diseases mostly involve people of European descent, which makes it hard to understand these diseases for everyone.
  • Out of 123 studies, 82% mainly included European participants, finding many genetic markers, while only a few were found in studies with non-European participants.
  • It’s super important to include more diverse backgrounds in future research to improve treatments and knowledge about these brain diseases.
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