News Archive

2024

Innate immune memory after stroke mediates secondary comorbidities.

July 2024 – ISD researchers hypothesized in a newly published study that the high rate of comorbidities that develop after a stroke could have a common immunological cause. A Myeloid innate immune memory was identified as causing remote organ dysfunction post-stroke. Single-cell sequencing revealed persistent pro-inflammatory changes in monocytes/macrophages up to 3 months after brain injury, especially in the heart, causing cardiac fibrosis and dysfunction. Neutralizing IL-1β or blocking monocyte trafficking prevented post-stroke cardiac dysfunction, suggesting immune-targeted therapies for secondary prevention. >>

Rational correction of disease-causing mutations in HTRA1

July 2024 – Rare mutations in HTRA1 cause cerebral vasculopathy and stroke. Using in vitro, in silico and in vivo analyses, the Dichgans lab in collaboration with colleagues from Duisburg established mechanistically distinct protein repair approaches to reverse the deleterious effects of pathogenic mutations interfering with the oligomeric assembly and protease function of HTRA1. Their findings exemplify the feasibility of rational strategies to correct protein conformations and open perspectives for precision medicine >>

ISD Research Retreat

July 2024 – ISD research teams gathered for the annual scientific retreat to present their projects and discuss science. The meeting included presentations from Ph.D. students, an evening poster session, invited speaker talks, and a three minute thesis competition. The meeting further served as an opportunity to familiarize people with the medium- and long-term strategy of ISD.

International Review by the ISD Scientific Advisory Board

June 2024 – Every two years, an international committee of scientific advisors evaluates ISD's research activities and makes recommendations for future direction. The first day of the meeting was dedicated to an in-depth review of three selected research groups. The second day featured an overview of research highlights presented through a series of presentations and poster sessions led by Postdoctoral Fellows and PhD students.

Rare and common HTRA1 variants affect stroke risk via two independent mechanisms

May 2024 – Combining genetic analyses in large international biobanks with experimental studies on human cells, ISD investigators found that rare HTRA1 variants affect vascular risk via a loss of enzymatic function of the HTRA1 protease, whereas a common causal variant independently affects vascular risk by influencing the circulating HTRA1 mRNA and protein levels. They further uncovered a complex relationship with other diseases including migraine and macular dystrophy. >>

30th Workshop of the International Stroke Genetics Consortium

April 2024 – The ISD is organising this year's International Stroke Genetics Consortium (ISGC) workshop, held on LMU campus at the St.-Vinzenz-Haus of LMU Hospital close to the city center from April 24 to April 26, 2024. Aside from Keynote Lectures and Scientific Sessions featuring original science presented by renowned experts in different scientific fields there are social activities and networking events that will allow participants to explore Munich’s rich history and culture>>

Advanced Brain Science Without Coding Expertise

April 2024 – Researchers at ISD and Helmholtz Munich introduce DELiVR, offering a new AI-based approach to the complex task of brain cell mapping. The deep learning tool democratizes advanced neuroscience by eliminating the need for coding expertise. DELiVR empowers biologists to efficiently explore disease-related spatial cell dynamics, fostering the development of precision therapies for enhanced patient care. >>

Dysregulation of vesicular transport pathways during BEC aging

March 2024 – A proteomic profiling study on brain endothelial cells (BEC) by ISD investigators reveals a dysregulation of key regulators of endocytosis and receptor recycling (most prominently Arf6), macropinocytosis, and lysosomal degradation during aging. The study identified changes undetected in transcriptomic studies such as an accumulation of vesicle cargo and receptor ligands including Apoe. | Data are accessible via an interactive database https://becaging.de/

Role of CXCL10 as a causal mediator in Atherosclerosis

February 2024 – Integrating genetic information from >520,000 individuals with data from plasma proteomics, the team of Marios Georgakis identified a proteomic signature of IL-6 signaling activation and mediators of its effects on cardiovascular disease. Their analyses suggest, that the interferon-γ-inducible chemokine CXCL10 is a potentially causal mediator for atherosclerosis in different vascular beds (coronary, cerebral, and peripheral arteries) and could serve as a promising drug target for atheroprotection. >>

Changes in synapses related to protein 43 (GAP-43) speed up the spread of tau in AD

January 2024 – A combined neuroimaging and biofluid biomarker study investigated whether synaptic changes are associated with accelerated tau spreading in Alzheimer’s disease (AD). Higher levels of the presynaptic protein GAP-43 speed up the spread of tau in AD. These findings by Nico Franzmeier (ISD) and others are relevant for developing treatments to slow down the progression of the disease. >>

2023

Decoding strokes silent saboteurs

December 2023 – A study by Josh Shrouder within the Plesnila lab, together with collaborators reveals how dysfunction of capillary pericytes aggravates no-reflow after ischemic stroke. These longitudinal in vivo results challenge the notion that pericytes are terminally susceptible to ischemia, and demonstrate how acute interventions targeting pericyte constriction could be harnessed to accelerate the restoration of capillary blood flow and improve stroke outcome. >>

Influence by Imitation

November 2023 – A study by the BernhagenLab and collaborators shows that specific plant proteins resemble human signaling proteins of the immune system and can bind to their receptors. While representing basic cross-discipline research, the work might have translational implications, as the receptors are drivers of cardiovascular diseases and inflammation.>>

Identifying optimal treatment windows for patients at risk of Alzheimer's

November 2023 – A study by Anna Steward and Nicolai Franzmeier reveals that ApoE4 carriers experience faster and earlier disease progression due to amyloid's impact on tau. These results urge earlier intervention for ApoE4 carriers who show reduced efficacy in response to anti-amyloid drugs. This insight, crucial for 40-60% of sporadic AD cases, suggests a potential shift in therapy approaches, advocating for tailored clinical studies to validate this new paradigm. >>

Martin Dichgans among „Highly Cited Researchers 2023”

November 2023 – Of the world’s population of scientists, Highly Cited Researchers™ are 1 in 1,000. The current list from Clarivate identifies researchers who demonstrated significant influence in their field through the publication of highly cited papers. >>

Frontline results of the TREAT-SVDs trial

October 2023 – Main results from TREAT-SVDs, an EU funded multicenter, open-label, randomised, crossover trial were presented at the European Stroke Organisation Conference (ESOC) in Munich and recently published in the Lancet Neurolgy. The results show that four weeks of treatment with amlodipine, losartan, or atenolol did not differ in their effects on cerebrovascular reactivity in people with sporadic small vessel disease but did result in differential treatment effects in patients with CADASIL. >>

2nd BRENDA-LEDUCQ Meeting, Munich, Germany

October 2023 – The meeting started with a lecture Fabrice Dabertrand, University of Colorado: “From impaired cerebral blood flow to cognitive impairment“. Following this, the Early Career investigators went downtown for a Munich Experience event. The following days were filled with stimulating discussion and new ideas for collaborations. The whole team is exicted about the work ahead.>>

Skull: A key new player in the neuro-immune axis

August 2023 – Neuroimmune interactions exhibit remarkable complexity, and exploring brain borders has gained significant attention in the quest for innovative approaches to diagnose, monitor, and treat brain pathologies. The recent discovery of connections between the skull and meninges has brought the skull into focus. A large collaborative research team led by the Erturk lab extensively examined the molecular and structural aspects of the skull in both mice and humans. Their findings demonstrated that skull inflammation can serve as an indicator of brain inflammation in patients suffering from diverse neurological disorders. >>

wildDISCO: A Revolutionary Whole Mouse Body Mapping Technique

July 2023 – Researchers at the Erturk lab have introduced wildDISCO, a groundbreaking method that utilizes standard antibodies to achieve deep penetration into the whole mouse body, generating high-resolution 3D atlases of neurons, immune cells, the vasculature, and lymphatic vessels. With unprecedented insights into anatomical and functional connections among multiple organs and systems, wildDISCO promises to revolutionize disease understanding, drug development, and medical education. >>

ISD Research Retreat

July 2023 – ISD research teams gathered for the annual scientific retreat to present their projects and discuss science. The meeting included presentations from Ph.D. students, an evening poster session, invited speaker talks, and focused workshops such as the one on AI by Hannah Spitzer. The meeting further served as an opportunity to familiarize people with the medium- and long-term strategy of ISD.

ESO Conference in Munich

May 2023 – The European Stroke Organisation Conference ESOC 2023 opened with a public awareness campaign and proceeded with an extensive scientific programme including the presentation of large international trials in plenaries, workshops, teaching courses and other formats. ISD researchers served as the local hosts and also presented results >>

STRIVE-2 Standards released

May 2023 – Small vessel disease (SVD) accounts for ~25% of strokes, more than doubles the risk of future stroke, and contributes to up to 45% of dementia cases. In 2013, STandards for ReportIng Vascular Changes on nEuroimaging 1 (STRIVE-1) categorised features of SVD that are visible on structural MRI and defined standards on multiple levels up to reporting. In an international effort with other experts ISD investigators now updated guidance on imaging of vascular changes in studies of ageing and neurodegeneration to create STRIVE-2 >>

3rd EMBO Workshop on Stroke-Immunology

May 2023 – The 3rd edition of "The EMBO Workshop on Stroke-Immunology" will take place from September 18 to 21, 2023 at Schloss Hohenkammer in the iconic country side of Munich. The meeting provides a unique environment for scientists at all career levels to access recent advances in the rapidly evolving field of stroke and neuroimmunology research and to expand on collaborations. >>

Emmy Noether Award to Marios Georgakis

March 2023 – The DFG awarded an Emmy Noether Award to Marios Georgakis for establishing an independent junior research group focusing on the inflammatory mechanisms driving atheroprogression. His team will analyze high-dimensional data aiming to discover novel anti-inflammatory drug targets for cardiovascular disease, map molecular and histological immunophenotypes associated with atheroprogression, and uncover imaging and circulating biomarkers of human atheroinflammation >>

First LEDUCQ Network Meeting in NY City

March 2023 – The first biannual network meeting will be held on March 26-28, 2023 in New York City. Principal Investigators will present their research programs while also giving Early Career Investigators an opportunity to introduce their work. The International Network of Excellence on Brain Endothelium: A Nexus for Cerebral Small Vessel Disease (BRENDA) is coordinated by Martin Dichgans and Frank Faraci (Iowa) and funded by the Leducq Foundation >>

Hertie Network of Excellence in Clinical Neuroscience approved for prolongation

January 2023 – The Hertie Foundation will continue funding for its Network of Excellence in Clinical Neuroscience. The program provides support to junior scientists (four from LMU and TUM) 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 their underlying mechanisms. >>

2022

3D spatial-omics technology to tackle complicated diseases.

December 2022 – Identifying subtle tissue changes at disease initiation or characterizing the molecular perturbations that trigger disease progression remains difficult in animal models or post-mortem human organs. To address this challenge, ISD investigators developed DISCO-MS, a 3D spatial-omics technology that combines methods of tissue clearing with cutting edge AI, robotics and proteomics technologies. They applied DISCO-MS to an Alzheimer’s disease mouse model and to atherosclerotic plaques in the human heart to identify spatial-molecular maps. >>

Martin Dichgans among „Highly Cited Researchers 2022”

November 2022 – Of the world’s population of scientists and social scientists, Highly Cited Researchers™ are 1 in 1,000. The current list from Clarivate identifies researchers who demonstrated significant influence in their chosen field or fields through the publication of multiple highly cited papers during the last decade. Their names are drawn from publications that rank in the top 1% by citations for field and publication year in the Web of Science™ citation index. >>

CD8+ T cells induce IFN-responsive oligodendrocytes & microglia in white matter aging

October 2022 – Among the hallmarks of brain aging is a decline in white matter volume and function. Using scRNA-seq, the Gokce and Simons labs characterized age-related oligodendrocyte and microglial states. They identified a population of interferon-responsive oligodendrocytes (IRO) and microglia (IRM) that localize near CD8+ T cells in white matter. Lack of CD8+ T cells prevented age-related cell loss in white matter. Their findings unravel a so-far unknown role of the adaptive immune system during brain aging >>

A shortcut to inflammasome activation

October 2022 – A rapid immune response to signals released from pathogens and injuries is critical for maintaining tissue integrity and restoring homeostasis. This response is largely mediated by the concerted action of pattern recognition receptors. Such cooperativity has been described for Toll like receptors (TLRs) and the NLRP3 inflammasome, but the underlying molecular mechanisms remain elusive. ISD investigators now demonstrate that IKKβ binds NLRP3 providing a shortcut to inflammasome activation for rapid immune responses >>

2nd funding period for ImmunoStroke consortium granted

October 2022 – The German Research Foundation (DFG) has decided to fund the DFG Research Unit "ImmunoStroke: From Immune Cells to Stroke Recovery“ with 4.6 Million € for a second funding period of 3 years. The consortium is coordinated by Arthur Liesz and spans across 4 German universities, bringing together researchers in Munich, Hamburg, Essen and Münster >>

Stroke genetics informs drug discovery and risk prediction across ancestries

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 >>

Leducq grant on Brain Endothelium in Cerebral Small Vessel 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 >>

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.