Single-cell sequencing

During many years of research on malignant diseases, scientists at Fraunhofer ITEM in Regensburg have gained special expertise in analyzing single cells from liquid biopsies. With some minor adjustments, they can apply – and have already applied – the established, partly automated technologies for single-cell DNA and RNA analysis from clinical samples to other cell types in order to characterize these in more detail and to make use of the information thus obtained, for example to identify biomarkers. The Fraunhofer researchers are also using this expertise to identify prognostic biomarkers for Alzheimer’s disease in the project ADIS – Early Diagnosis of Alzheimer's Disease by Immune Profiling of Cytotoxic Lymphocytes and Recording of Sleep Disturbances. Fraunhofer ITEM is one of seven partners in the ADIS project, which is being funded by the EU Joint Program for Neurodegenerative Diseases Research (JPND) for three years with a budget of 1.3 million euros.

Alzheimer's disease and related dementias are heterogeneous, multifactorial diseases in which several etiopathogenic mechanisms lead to neuronal cell death and loss of cognitive function. The disease is believed to begin decades before diagnosis, posing a significant treatment challenge. Therefore, the identification of prognostic biomarkers for Alzheimer’s disease is of great importance. There is growing evidence that the systemic immune system is involved in the pathophysiology of Alzheimer’s. Using a multidisciplinary approach to multi-omics profiling of the immune system in conjunction with AI and agent-based modeling (ABM), novel signatures of the immune system and digitally recorded physiology shall be identified to facilitate early prediction of the disease. The aim is to enable improved therapies in the future.

Researchers at Fraunhofer ITEM in Regensburg will thoroughly characterize peripheral blood mononuclear cells (PBMCs) derived from samples taken from Alzheimer's patients, healthy volunteers, and patients with mild cognitive impairment, and will analyze their functional status. They will use combined single-cell immune repertoire and transcriptome sequencing for this. Two main analyses will be conducted to this end: (1) standardized combined generation and quality control of single-cell sequencing libraries for whole-transcriptome analysis and T cell receptor analysis, and (2) single-cell RNA sequencing of PBMCs to identify immune subpopulations that are uniquely associated with Alzheimer's disease, with a focus on natural killer cells and effector memory cells.