July 2021 – Age-related loss of white matter integrity is a major determinant of cognitive decline and dementia. Analysing data from >30.000 UK Biobank participants, ISD investigators in collaboration with Matthew Traylor (London) found the complement component C4-BS variant to associate with age-related WM injury. These findings suggest a role of the complement systems and of gene-environment interactions in age-related loss of white matter microstructural integrity...
July 2021 – Michael Ewers received the prestigious 2021 de Leon Prize for Neuroimaging awarded at the Alzheimer Association International Conference in Denver. The de Leon Prize in Neuroimaging recognizes senior scientists and is shared with Dr. Juan Fortea, Spain...
June 2021 – ISD researchers found that a common variant in the anti-aging gene KLOTHO is associated with reduced fibrillar tau, a key pathology in Alzheimer’s disease...
March 2021 – Leveraging data from the UK Biobank (N=229,976 participants) ISD investigators examined whether cardiovascular health measured by the ‘Life’s simple 7’ score is associated with incident all-cause dementia. They found that higher blood pressure was associated with higher risk of dementia both in longitudinal and Mendelian Randomization analyses. These findings underscore the importance of blood pressure control in midlife to mitigate dementia risk...
March 2021 – Drugs targeting IL6 signaling have been approved for autoimmune diseases but the repurposing potential for other indications remains unknown. ISD researchers developed a genetic score predicting IL6 signaling activity over lifetime. In a phenome-wide association study they found genetically downregulated IL6 signaling to be associated with a favourable cardiometabolic profile including a lower risk of coronary artery disease and diabetes, and an increase in HDL cholesterol levels. Their results support repurposing of IL6R blockade as a strategy for lowering vascular risk...
March 2021 – Stroke patients are predisposed to life-threatening infections after the initial ischemic event. This phenomenon is caused by a severe state of post-injury immunosuppression, which is characterized by a loss of T cells. Stefan Roth (Liesz Lab) in collaboration with others demonstrates that monocytes sense injury-released cell-free DNA via the AIM2 inflammasome inducing extrinsic T cell death. Uncovering this mechanism could open up new therapeutical approaches...
Sarah Jäkel joins ISD as a Junior Group Leader
March 2021 – As an Emmy Noether awardee, Sarah Jäkel explores the role of oligodendrocytes – the myelin forming cells in the central nervous system – in the pathogenesis of Alzheimer’s disease. Applying cutting-edge transcriptomic approaches such as single-nuclei RNA-sequencing to postmortem human brain tissue as well as two and three-dimensional human stem cell-derived oligodendrocyte cultures as model systems, she aims to characterize the functional oligodendrocyte cell states that she recently described and unravel their individual contribution to disease...
March 2021 – Co-organized by Arthur Liesz (ISD) and Adam Denes (Budapest) the 1st Stroke-Immunology Conference was hosted fully virtual. The meeting was attended by 470 participants from 23 countries with contributions from 34 live speakers and 32 pre-recorded webcasts. The aim of this conference was to convene scientists working on inflammatory mechanisms in acute brain ischemia with leading experts on related research topics in neuroimmunology, neuroscience and neuroimaging. The meeting will be continued in 2022 and is scheduled for March 9-11th in a hybrid format.
White matter aging drives microglial diversity
February 2021 – Aging and vascular risk factors are associated with white matter (WM) lesions and loss, but the role of microglia in the aging WM has been elusive. Using single-cell RNA sequencing, ISD and DZNE investigators identified WM-associated microglia (WAMs), which form in a TREM2-dependent but APOE independent manner and are characterized by age-dependent activation of genes implicated in phagocytic activity and lipid metabolism. Thus, WAMs may represent a potentially protective response required to clear degenerated myelin accumulating during WM aging and disease...
Bayer Early Excellence in Science Award for Nicolai Franzmeier
December 2020 – Nicolai Franzmeier is being recognized with the 2020 Bayer Early Excellence in Science Award in Medical Sciences, which is awarded by the Bayer foundation to excellent young scientists and physicians in the early stages of their academic and clinical research careers. He received the award for developing novel neuroimaging tools to investigate Alzheimer’s disease progression, showing that tau pathology, i.e. the key driver of cognitive decline, spreads across brain networks...
Patient-centered prediction of tau spreading in Alzheimer’s
Designed chemokine receptor mimic blocks atherosclerosis by chemokine-specific targeting
November 2020 | Atherosclerosis is the main cause of stroke and myocardial infarction. While the inflammatory paradigm is established, the development of anti-cytokine/chemokine therapeutics for atherosclerosis has remained challenging. A team of investigators led by the Bernhagen (ISD) and Kapurniotu (TUM) labs designed peptide-based mimics of the chemokine receptor CXCR4 that block experimental atherosclerosis. The new compounds selectively target pro-atherogenic chemokine pathways, whereas homeostatic pathways are spared. The study is published in Nat Communications...
Complicated Carotid Artery Plaques as a Cause of Cryptogenic Stroke
November 2020 | In up to 30% of patients the aetiology of stroke remains unknown. Applying high-resolution contrast-enhanced carotid MRI to patients with acute ischemic stroke ISD investigators identified nonstenosing complicated carotid artery plaques (cCAP) as an underrecognized cause of stroke. The most frequent feature of ipsilateral cCAP was intraplaque haemorrhage (89%), which can be reliably detected by conventional MRI sequences. Whether integrating carotid MRI into the diagnostic workflow would add clinical decision-making remains to be explored...
Neuropilin-1 opens the door to SARS-CoV-2 cell entry and infectivity
November 2020 | An international research team, coordinated by Mikael Simons (DZNE) with participation of the Gokce Lab identified neuropilin-1 as a factor that facilitates SARS-CoV-2 entry into cells including of the central nervous system. The study is now published in “Science”.
Diffusion MRI alterations in the elderly are predominantly of vascular origin
August 2020 | Diffusion tensor imaging is widely used to study the brain microstructure, especially in memory clinic patients. The determinants of diffusion alterations are, however, largely unknown. A large-scale study led by ISD investigators addresses this important question by identifying cerebral small vessel disease as the main determinant of diffusion alterations...
Chan Zuckerberg Initiative (CZI) Award for Ozgun Gokce
August 2020 | Ozgun Gokce group leader at the ISD received the CZI Neurodegeneration Challenge Network (NDCN) Collaborative Pairs Pilot Projects award together with Michael Simons (DZNE-Munich). This new grant represents the next phase of the CZI Neurodegeneration Challenge Network (NDCN) an interdisciplinary collaborative network launched in December 2018. The funding is aimed to support initial pilots for innovative exploratory ideas. Successful projects and teams will receive further funding in the 2nd phase pending scientific review...
Higher sTREM2 and microglia PET associated with lower amyloid accumulation.
August 2020 | Alterations in the brain’s immune response are associated with higher risk of Alzheimer’s dementia, but the effect of microglia activation on amyloid-plaque deposition is elusive. ISD and DZNE investigators found higher CSF sTREM2 and TSPO PET, i.e. biomarkers of microglia activation, to be associated with lower amyloid accumulation in both mouse models of amyloid deposition and elderly individuals, suggesting a protective effect of TREM2-related microglia activity against a key Alzheimer’s pathology...
Junior Research Group Award for Steffen Tiedt
August 2020 | Steffen Tiedt, a clinician-scientist at the ISD, was awarded 1.0M € by the Corona-Foundation for a research program on “Precision Medicine in Stroke (PROMISE)”. The support will enable him to establish a Junior Research Group that will focus on identifying circulating molecular signatures by profiling samples both from stroke patients and mouse models. Such signatures could aid stroke diagnostics and enhance our understanding of stroke pathophysiology...
Metabolic signature differentiates ischemic stroke from stroke mimics
August 2020 | Early discrimination of patients with ischemic stroke (IS) from stroke mimics (SM) is important to allocate treatments, but poses a diagnostic challenge. Applying untargeted metabolomics to serum samples from > 800 patients with stroke-like symptoms, ISD investigators identified a signature of circulating metabolites that differentiates IS from SM with higher accuracy than multimodal cranial computed tomography upon hospital admission...
Visualization of biocompatible nanoparticles
July 2020 | Biocompatible nanoparticles have huge therapeutic potential, but could so far not be visualized. In a collaboration with investigators from Strasbourg, Igor Khalin (Plesnila Lab) now demonstrates that specifically designed ultra-bright nanoparticles can be traced in vivo by 2-photon microscopy. This technological breakthrough greatly improves our understanding how to target therapeutic compounds to the CNS...
Rolf-Becker Prize 2020 awarded to ISD scientist
July 2020 | Ali Erturk was awarded with the "Rolf-Becker"-Prize for one of the best scientific outputs in 2019/2020 by the Medical Faculty of LMU Munich. He received this prestigious award for his work on Deep Learning revealing therapeutic antibody targeting in the entire body published in CELL...
HDAC9 – from GWAS discovery to mechanisms and therapeutic targeting
June 2020 | Drug targets with support from human genetics have a higher probability of reaching phase III clinical trials and regulatory approval. Following their GWAS-based discovery of HDAC9 as a major risk locus for human atherosclerosis, ISD investigators identified a detailed mechanism linking HDAC9 to vascular inflammation. They further demonstrate that therapeutic inhibition of this HDAC9-dependent pathway confers plaque stability on top of atheroprotection …
Martin Dichgans to serve ESO as its President
June 2020 The European Stroke Organisation (ESO) has rapidly grown to become a driving force in convening stroke researchers around the globe, promoting research and educational events and optimising stroke care in Europe and beyond. Starting in May 2020 Martin Dichgans currently serves ESO as its new President. His focus will be on promoting the development of the ESO Guidelines and further strengthening ESOs role within the community
Taming widespread collateral damage of CRISPR editing
May 2020 CRISPR-Cas9 has revolutionized disease-research, as it greatly simplifies targeted genome editing. However, CRISPR systems are not entirely accurate and can introduce potentially harmful additional mutations, called on-target effects. In a collaborative study with the DichgansLab, the PaquetLab identified widespread prevalence of on-target effects in clinically relevant CRISPR-edited iPS cells and describes broadly applicable tools to detect these unintended alterations. The new method improves the reliability of CRISPR editing...
Machine learning analysis of whole mouse brain vasculature
March 2020 The Ertürk lab in collaboration with others (ISD, Helmholtz Munich and TUM) developed an artifical intelligence aided tool to study the vasculature in complete transparent mouse brains. Using 3D microscopy, they visualized the underlying complex network of all brain vessels at the capillary level. Their new tool can generate reference maps of the adult mouse brain vasculature, which could be used to model synthetic cerebrovascular networks. On this basis, unknown vascular properties can be discovered and biological models can be confirmed...
Aβ deposition associated with white matter alterations in cognitive normal people
March 2020 In an international collaboration, ISD researchers report increased amyloid PET uptake to be associated with higher age-related fiber tract alterations and white matter hyperintensities in cognitively asymptomatic people...
February 2020 The Ertürk lab (ISD and Helmholtz Munich) managed to make intact human organs transparent. Using microscopic imaging they visualized underlying complex structures of see-through organs at the cellular level. Resulting organ maps could serve as templates for 3D-bioprinting technologies. This eventually could contribute to the creation of on demand artificial organs for patients in need...
Digital medicine model of cognitive worsening in Alzheimer’s disease
February 2020 In a large collaborative study with the North American DIAN and ADNI studies, ISD researchers developed a fully automated and cross-validated machine-learning algorithm for the prediction of disease progression in Alzheimer’s disease. The biofluid and neuroimaging derived model allows to predict the rate of cognitive decline over a clinically relevant time window of 4 years….
January 2020 Using Mendelian Randomization ISD investigators showed that genetic predisposition to higher HDL-C, specifically to cholesterol in medium-sized HDL, is associated with small vessel stroke and white matter injury. Their analyses indicate that HDL-C-raising strategies could be considered for the prevention of ischemic small vessel disease but the net benefit of such an approach needs to be tested in a randomized controlled trial...
Tau spreading associated with functional connectivity in Alzheimer’s disease
January 2020 A multinational study led by the Ewers Lab and first author Nicolai Franzmeier shows that functional brain architecture predicts the spatial patterns of the gradual spreading of tau pathology in Alzheimer's disease, supporting in-vitro findings of trans-neuronal tau propagation...
December 2019 ISD researchers developed a metaGRS for ischaemic stroke (IS) that outperforms previous GRS and identifies a subset of individuals at monogenic levels of risk. Individuals in the top 0.25% of the metaGRS have a threefold increased risk of IS. The results suggest that, for individuals with a high metaGRS, achieving risk factor levels recommended by current guidelines may be insufficient to mitigate risk...
December 2019 Combining clearing technology with deep learning algorithms ISD investigators developed an integrated pipeline for automated quantification of cancer metastases and therapeutic antibody targeting (DeepMACT) that enables analysing the size, shape, and spatial distribution of metastases, and the degree to which metastases are targeted by therapeutic monoclonal antibodies in entire mice...
December 2019 Ali Ertürk received a prestigious ERC Consolidator Grant for his research project CALVARIA ‘Translational Aspects of the Discovery of Skull-Meninges Connections’. SMCs where recently discovered by Ali Ertürk and others and enable immune cells to migrate into the brain suggesting they could play a role in brain disorders including stroke and dementia ...
Hertie Network of Excellence in Clinical Neuroscience
November 2019 Neuroscientists at LMU and TUM have been awarded members of the Hertie Network of Excellence in Clinical Neuroscience. The program provides support of junior scientists and facilitates collaborations across participating sites. The scientific focus of the Munich site (Speakers: M. Dichgans and Thomas Korn) is on neurovascular, neurodegenerative, and neuroinflammatory diseases and underlying mechanisms...
Medical Excellence fellowship for ISD Researcher
November 2019 Philip Melton, MD student in the Liesz lab, was awarded the „Medical Excellence“ Fellowship 2019 in the field of Neuroscience for „StrokeMicroBiomics“. The project explores long-term microbiome dysbiosis and metabolomic changes in stroke patients...
Circulating MCP-1 levels associate with stroke risk
September 2019 Expanding on their previous Mendelian Randomisation study (CIRCULATION 2019) ISD researchers now provide further evidence for a causal role of MCP-1 in stroke. In a meta-analysis of observational data from 17,180 stroke-free individuals they found higher circulating MCP-1 levels to be associated with long-term risk of incident ischemic stroke...
Protective effects of TREM2 in Alzheimer's Disease
August 2019 The teams of M. Ewers and C. Haass found higher cerebrospinal fluid comcentrations of TREM2, a biomarker of microglia activation, to slow down cognitive decline in Alzheimer's Disaease...
Novel insights into small vessel disease progression
July 2019 Using a prospective, high-frequency serial imaging study, a team of researchers at ISD and Radboudumc Nijmegen identified acute infarcts as the cause of incident lacunes and almost a third of incident microbleeds. In contrast, the progression of white matter hyperintensities was independent from acute infarcts. These new insights were enabled through a unique study design with monthly MRI exams...
ISD Research Retreat
July 2019 July 10th and 11th ISD research teams met for the yearly scientific retreat to present their projects and discuss the science. At the heart of this meeting were presentations from all Ph.D. students, including an evning poster session. The last year brought about important achievements both scientifically and with regard to expertise and infrastructure. The meeting further served as an opportunity to familiarize people with the medium- and long-term strategy of ISD...
July 2019 The project led by Christian Grimm (Walther‐Straub‐Institute) and Dominik Paquet (ISD) is supported with 86.000 Euros by the German Neuronal Ceroid Lipofuscinosis Foundation (NCL) and aims to develop novel treatment strategies for childhood dementia...
April 2019 A multinational study led by Michael Ewers and his team suggests that enhanced tau pathology may underlie the increased risk of Alzheimer’s conferred by the BIN1 single nucleotide polymorphism - the second most important genetic risk factor of AD...
April 2019 ISD researchers found a common variant in the BDNF gene to modulate the impact of amyloid pathology on hippocampal network connectivity and memory in Alzheimer’s disease...
March 2019
Congratulations to our longstanding collaborators Marie-Germain Bousser, Anne Joutel, Hugues Chabriat, & Elisabeth Tournier-Lasserve (Paris, Fr.) for receiving the prestigious BRAIN price. Their groundbreaking work on CADASIL has profoundly influenced the understanding of cerebral small vessel disease & vascular cognitive impairment...
February 2019
A combined fMRI and tau PET study in Alzheimer’s disease by Michael Ewers and team shows that the spatial pattern of tau pathology is predicted by functional network connectivity, suggesting that cross-talk between brain regions is conducive to tau spreading...
January 2019
The Erturk group developed a nanobody-based immunolabeling method, vDISCO, that enables imaging subcellular details in transparent mice. They uncovered neuronal projections and skull–meninges connections in whole adult mice that are likely to have relevance in both health and disease...
November 2018
Ali Ertürk has been awarded $715.000 from NIH (USA) to explore the role of brain lymphatic/glymphatic systems in dementia and ageing in collaboration with Maiken Nedergaard (Rochester University, New York)...
A genome-wide meta-analysis involving almost 900.00 subjects from the MEGASTROKE consortium and UK Biobank identified new risk loci for stroke among them endothelial nitric oxide synthase (NOS3). The study further suggests that genetic variation in the NOS - nitric oxide (NO) pathway in part affects stroke risk via variation in blood pressure...
October 2018
ISD investigators in collaboration with researchers from France found that MoCA, a brief cognitive test, when taken within a week after stroke predicts the risk of cognitive impairment, functional impairment and mortality up to 3 years later. The findings inform clinical practice by highlighting the need of early cognitive screening after stroke...
September 2018
Using a Mendelian Randomization approach and data from >800.000 individuals ISD investigators showed that genetic predisposition to higher levels of the inflammatory cytokine MCP-1 is associated with a higher risk of stroke, in particular large artery stroke and cardioembolic stroke. These findings inform the planning of future clinical trials...
The first funding decisions in the context of the Excellence Strategy have been announced. Four Clusters of Excellence including the Munich Cluster for Systems Neurology (SyNergy) submitted by LMU and TUM were successful and will receive funding from 2019 on...
Ewers and his team found the evolution of white matter alterations to start in callosal fibers already 10 years before estimated symptoms onset in familial Alzheimer’s disease...
August 2018
Chenchen Pan from Ali Ertuerk's group received the Chinese government award for outstanding self-finance students abroad. Established by the China Scholarship Council in 2003 the award is considered the highest recognition given by the Chinese government to graduate students abroad who do not receive financial support from the Chinese government...
July 2018
A prestigious ERC Starting Grant was awarded to the ISD researcher Arthur Liesz for the project „RecoverInFlame“. The 1.5M € award by the European Research Council (ERC) will support the Liesz lab to investigate inflammatory mechanisms in the recovery after acute stroke...
Stefan Roth and Dr. Arthur Liesz were awarded with the "Rolf-Becker"-Prize for one of the best scientific outputs in 2017/18 by the Medical Faculty of LMU Munich and the foundation "Rufzeichen Gesundheit!" Baierbrunn. They received this prestigious award for their recent work published in Science Translational Medicine...
May 2018
A large scale genetic study on major brain diseases including stroke and Alzheimer's disease revealed shared genetic influences between multiple brain disorders and relevant phenotypes, including cognitive measures. The results highlight the value of heritability-based methods in understanding the ethiology of neurological and psychiatric disorders. ISD investigators were on the steering committee of this work which was published in Science...
The Collaborative Research Center SFB1123 „Atherosclerosis – Mechanisms and Networks of Novel Therapeutic Targets" has been approved a second funding period. The ISD contributes to the LMU led network with two projects, headed by Martin Dichgans/Yaw Asare (project B5) and Jürgen Bernhagen (project A3), as well as flanking project C1 (Arthur Liesz)...
Steffen Tiedt, a clinician scientist at the ISD has been awarded the Young Investigator Award 2018 by the European Stroke Organisation (ESO) for his work on serum Neurofilament Light as a marker for neuroaxonal injury after stroke...
Complex heart surgery may lead to organ dysfunction such as acute kidney injury (AKI) or ischemic stroke. A researcher team led by Aachen University and the Bernhagen lab found that patients with high blood levels of the cytokine MIF had a reduced risk of developing AKI. The study is published in this week’s issue of Sci Transl Med...
Isolation of CADASIL patient brain vessels in combination with proteome analysis identified loss of HTRA1 proteolytic function as a critical step in the development of disease pathology providing novel insights into the molecular mechanisms of cerebral small vessel diseases....
Apr 2018
The Bernhagen lab at ISD together with collaborating labs uncovered a previously unrecognized connection between the atherogenic chemokine-like cytokine MIF and B cell function in atherosclerosis...
Mar 2018
Munich, March 21-23, the European Stroke Organisation (ESO) in collaboration with the Stroke Alliance for Europe (SAFE) convened leading experts in stroke research and care to an international workshop targeted at identifying current challenges in the prevention and treatment of stroke, set the goals for the next decade...
