ADIS stands for "Early Diagnosis of Alzheimer's Disease by Immune Profiling of Cytotoxic Lymphocytes and Recording of Sleep Disturbances." The project is funded by the EU Joint Programme for Neurodegenerative Diseases Research (JPND). JPND is the largest global research initiative to address neurodegenerative disease challenges. The ADIS project (start: July 2022) will run for three years and has a budget of 1.3 million euros, of which 300,000 euros will go to Fraunhofer SCAI.

Alzheimer's disease (AD) 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 thought to begin decades before diagnosis, posing a significant treatment challenge. Therefore, the identification of prognostic biomarkers for AD is of great importance.  

There is growing evidence that the systemic immune system is involved in the pathophysiology and treatment of AD. Understanding the mechanisms linking cognitive impairment, sleep disturbances, and inflammation could facilitate earlier diagnosis of the disease.

The project will characterize cytotoxic lymphocytes in peripheral blood as potential markers for predicting AD and investigate the impact of sleep disturbances on these markers. ADIS 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. The project uses a multidisciplinary approach to multi-omics profiling of the immune system in conjunction with AI and Agent-Based Modeling (ABM).

Further goals of ADIS are to:

(a) provide new candidate biomarkers and insights into the role of peripheral cytotoxic lymphocytes (specialized immune cells in the blood) in AD; and

(b) understand the correlation of immune signatures with digitally recorded pathophysiological disorders, such as cognition and sleep.

To this end, the project will collect a large amount of data using single-cell sequencing, flow cytometry, clinical examination, as well as modern digital technologies (augmented reality application, smartwatch), from

• 25 healthy individuals, 
• 25 individuals with mild cognitive impairment due to Alzheimer's disease, and 
• 25 people with mild to moderate Alzheimer's disease.

Fraunhofer SCAI is involved in various tasks in ADIS:

• Project coordination
• Organization of legally compliant access to the data
• Integration of the newly collected data into an existing data catalog
  
• Statistical analysis of the data
• Development of AI models to achieve a more detailed understanding of the interplay of biological, immunologically relevant mechanisms with pathophysiological symptoms of the disease. This could contribute to earlier diagnosis of AD in the future.
   

Project Coordination

• Prof. Dr. Holger Fröhlich, Fraunhofer SCAI
• Vanessa Lage-Rupprecht, Fraunhofer SCAI
   

Project Partners and Principal Investigators

• Dr. Raquel Sanchez-Valle, Fundació Clínic per a la Recerca Biomèdica (FCRB)
• Prof. Dr. Uri Nevo, Tel Aviv University (TAU)
• Jean Georges, Alzheimer Europe (AE)
• Dr. Stefan Kirsch, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM-R)
• Dr. Istvan Nagy, SeqOmics Biotechnology Ltd (SO)
• Dr. Eti Yoles, ImmunoBrain Checkpoint LTD (IBC)
   

Acknowledgment

This project is supported in Germany through the BMBF (Funding reference 01ED2206A) under the aegis of the EU Joint Programme – Neurodegenerative Disease Research (JPND) – www.jpnd.eu

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