Fraunhofer ITEM research targeting early Alzheimer’s diagnosis

Biomarkers and algorithms are to enable minimally invasive and cost-effective early diagnosis of Alzheimer‘s disease

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.

This challenge has been taken up in the project ADIS – Early Diagnosis of Alzheimer’s Disease by Immune Profiling of Cytotoxic Lymphocytes and Recording of Sleep Disturbances – in which Fraunhofer ITEM is one of seven project partners. ADIS is being funded by the EU Joint Program for Neurodegenerative Diseases Research (JPND) for three years, with a budget of 1.3 million euros.

Involvement of the systemic immune system

There is growing evidence that the systemic immune system is involved in the pathophysiology of Alzheimer’s. Understanding the mechanisms linking cognitive impairment, sleep disturbances, and inflammation could facilitate earlier diagnosis of this disease. Using a multidisciplinary approach to multi-omics profiling of the immune system in conjunction with AI and agent-based modeling (ABM), the project aims to identify novel signatures of the immune system and digitally recorded physiology for early prediction of the disease, potentially occurring early in the disease course and associated with rapid clinical decline.

Fraunhofer ITEM researchers 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 analyze their functional status. They will use comparative 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.

The Fraunhofer ITEM researchers in Regensburg are experts when it comes to high-quality, in-depth characterization of target cells at the single-cell level based on very small quantities, and also in deriving information from these analyses, for example to identify biomarkers. The scientists have comprehensive experience with miniaturized and automated RNA and DNA analysis of single cells from clinical samples.

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