News

September 2022 – A GWAS meta-analysis of >110,000 stroke patients and 1.5 Mio controls from five different ancestries identified multiple novel stroke risk loci. The study provides genetic evidence for putative drug effects with converging evidence for drugs targeting F11 and KLKB1 among others. Drugs targeting F11 and F11a are currently being examined in phase II trials for stroke prevention. A polygenic score predicted ischemic stroke across ancestries and in clinical-trial participants with cardiometabolic disease >>

September 2022 – The Leducq Foundation has chosen to fund an International Network of Excellence on Brain Endothelium: A Nexus for Cerebral Small Vessel Disease (BRENDA) with 7.5 M USD over five years. The Network is coordinated by Martin Dichgans and Frank Faraci (University of Iowa, USA) and involves further investigators from Germany, Sweden, France, and the USA >>

July 2022 – ISD research teams met for the annual scientific retreat to present their projects and discuss the science. At the heart of this meeting were presentations from Ph.D. students, including an evening poster session, a guest talk by Nobel price laureate Reinhard Genzel, and focused workshops. The meeting further served as an opportunity to familiarize people with the medium- and long-term strategy of ISD.

June 2022 – The Collaborative Research Center CRC1123 “Atherosclerosis - Mechanisms and Networks of Novel Therapeutic Targets” was awarded a 3rd funding period until 2026. The cluster encompasses 20 projects. ISD scientists participate in projects A2 (Hundelshausen/Bernhagen), A3 (Bernhagen/Kapurniotu), B3 (Asare, Dichgans), B11 (Liesz/Sager). J. Bernhagen is the Vice-Spokesperson. CRC1123 aims to elucidate the mechanisms and molecular networks driving atherosclerosis and further the identification of therapeutic target candidates >>

May 2022 – Complicated nonstenosing carotid artery plaques (CAPs) are an under-recognized cause of stroke. Applying high-resolution contrast-enhanced carotid MRI to patients with acute ischemic stroke, ISD investigators found complicated CAP ipsilateral to acute ischemic anterior circulation stroke to be associated with an increased risk of recurrent ischemic stroke or TIA. Carotid plaque imaging identifies high-risk patients who might be suited for inclusion into future secondary prevention trials >>

March 2022 – Tau pathology drives neuronal dysfunction in 4-repeat tauopathies. Here, ISD researchers combined tau-PET, resting-state fMRI and histopathology data, to show that brain connectivity is associated with tau deposition patterns in patients with 4-repeat tauopathies >>

February 2022 – The EMBO Workshop on Stroke-Immunology running 9 – 12 March in Munich, Germany, will provide a platform for uniting experts in the field with leading scientists from related research areas, including immunology, neuroscience, and advanced research tools. This shall facilitate close interactions and lasting relationships between established scientists in this emerging research area with leaders in related fields, accelerating further developments in stroke-immunology >>

November 2021 – The Leducq Foundation - a charitable organization that funds collaborative research in cardiovascular disease and stroke – awarded a new trans-atlantic network of excellence on circadian effects in stroke (coordinators: Eng Lo, Boston, & Alastair Buchan, Oxford). Together with basic, translational, and clinical scientists in the USA, UK, and Spain, the ISD (PI: S. Tiedt) now seeks to understand how circadian biology affects stroke pathophysiology with the ultimate aim to identify novel therapeutic targets for stroke >>

October 2021 – The Bernhagen (ISD) and Kapurniotu (TUM) labs are among the awardees of this year’s m4 competition for innovative biomedical projects by the Bavarian State Ministry of Economic Affairs. Despite significant progress, atherosclerotic disease (stroke and myocardial infarction) remains the leading cause of death. Tackling residual inflammatory risk has evolved as a promising preventive strategy. The m4 award will enable the team to develop chemokine receptor mimics as drug leads to selectively inhibit key atherosclerosis-causing chemokine >>

October 2021 – In a whole-exome sequencing study on >16.000 individuals, ISD investigators found rare variants in the protease domain of HTRA1 to associate with brain WMH burden. The frequency of such variants in the general population was 1:450 and their presence corresponded to a larger effect than meeting the criteria for conventional vascular risk factors. Variants in EGFL8, which falls into a common pathway with HTRA1, also associated with WMH burden >>

September 2021 – CSDs are the electrophysiological correlate of migraine aura and involved in the propagation of brain damage after ischemic and traumatic brain injury. Using a novel migraine mouse model, the Plesnila Lab in collaboration with Tobias Freilinger, Holger Lerche (Tübingen, Germany), and Massimo Mantegazza (Nice, France) found that CSDs are triggered by inhibitory interneurons. This counterintuitive finding unravels the so far unknown cellular mechanism for the initiation of CSDs >>

Role of complement component C4 in age-related white matter injury

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 >>

de Leon Senior Scientist Prize for Michael Ewers

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...

Common KLOTHO SNP protects against Tau pathology

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...

Life’s simple 7 and incident dementia risk

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...

Genetic downregulation of IL-6 signaling leads to a favourable cardiometabolic profile

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.