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Scientists at the Institute of Anatomy at Leipzig University, working together with international research institutions, have identified a previously unknown group of immune cells in the brain tissue of people with Alzheimer’s disease. This discovery was made possible by a newly developed microscopy technique that has, for the first time, been specifically optimised for the human brain. The findings have been published in the prestigious journal Nature Neuroscience.
Microglia are the brain’s specialised immune cells and fulfil a role similar to that of the immune system elsewhere in the body. For years, they have been a major focus of research into neurodegenerative diseases such as Alzheimer’s, as they appear to play a role in how these conditions develop and progress. Previous studies in animal models have already identified subgroups of these cells that become particularly active during disease. However, key influencing factors such as ageing cannot be replicated adequately in animal models, making research using human brain tissue essential. The new study helps to bridge this gap. In an international collaboration with the research group led by Professor Bahareh Ajami at Oregon Health and Science University in Portland, researchers at the Institute of Anatomy at Leipzig University investigated where and to what extent these specialised microglial cells are present in brain samples from people with Alzheimer’s disease.
Using a novel spatial single-cell analysis technique, the team was able for the first time to characterise microglia in the human brain in detail at protein level. “By analysing brain tissue from body donors, we identified a previously unknown cell population that is closely linked to specific protein deposits in the tissue and occurs far more frequently in the brains of Alzheimer’s patients. Our findings also show that microglial cells adopt different specialised states in the Alzheimer’s brain,” says Dr Dennis-Dominik Rosmus, a researcher at the Institute of Anatomy at Leipzig University and one of the three lead authors of the publication.
For the study, the researchers further developed an advanced microscopy technique known as the CODEX method, which allows multiple protein markers to be analysed simultaneously within tissue samples. The technique was specifically optimised for use in human brain tissue and combined with newly developed bioinformatic analysis methods. The resulting CODEX-CNS method can analyse complex cell structures within their spatial environment. By combining protein profiles, cell morphology and the relationships between neighbouring cells, the method can identify cell populations that are often missed by more conventional, less comprehensive approaches. The findings were also validated using immunofluorescence staining on brain sections from Alzheimer’s patients held in the brain bank at the Leipzig Institute of Anatomy.
The study provides important new insights into the biological mechanisms underlying Alzheimer’s disease. A better understanding of how the brain’s immune cells respond to protein deposits and cellular damage could, in the long term, help pave the way for the development of targeted therapies. The research group now plans to further develop the CODEX-CNS method and apply it to other neurological diseases. One of the key challenges for future studies will be to detect the identified cell populations in living patients as well, for example by using nuclear medicine imaging techniques.
Translation: Matthew Rockey
Dr. med. Dennis-Dominik Rosmus
Resident physician, Department of Neurology, University of Leipzig Medical Center
Researcher, Institute of Anatomy, Leipzig University
Email: dennis-dominik.rosmus@medizin.uni-leipzig.de
Original publication in Nature Neuroscience: Spatial proteomic analysis in human Alzheimer’s disease brains enables identification of microenvironment-dependent microglial cell states. DOI: https://doi.org/10.1038/s41593-026-02267-3
The different cell populations in the human brain are shown in different colours, with microglial ce ...
Quelle: figure: Dennis-Dominik Rosmus
Copyright: Sanchez-Molina, Rosmus, Brownell et al., Nature Neuroscience, 2026.
Dr. med. Dennis-Dominik Rosmus
Quelle: Martin Musiol
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The different cell populations in the human brain are shown in different colours, with microglial ce ...
Quelle: figure: Dennis-Dominik Rosmus
Copyright: Sanchez-Molina, Rosmus, Brownell et al., Nature Neuroscience, 2026.
Dr. med. Dennis-Dominik Rosmus
Quelle: Martin Musiol
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