ISD Research Retreat
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.
CRC1123 “Atherosclerosis” approved for another 4 years
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 >>
Complicated Carotid Artery Plaques and Risk of Recurrent Ischemic Stroke or TIA
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 >>
Brain connectivity is associated with tau deposition in 4-repeat tauopathies
EMBO Workshop - Stroke-Immunology
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 >>
Leducq grant on circadian mechanisms in stroke
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 >>
m4 Award for Bernhagen Lab
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 >>
Role of HTRA1 in brain white matter hyperintensities
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 >>
Interneurons trigger cortical spreading depolarizations (CSDs)
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
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...
AIM2-inflammasome signaling cascade causes post-stroke immunosuppression and secondary infections
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...
First International Stroke-Immunology Conference | Online
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...