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Alzheimer's Association International Conference 2026
July 12-15, 2026 | London, United Kingdom, and Online
7061
Immune Signatures In Cytotoxic Lymphocytes Linked To Sleep Disturbances And Cognitive Decline In Early Alzheimer's Disease
Poster Presenter
Authors
Part of Topic
Immune Signatures In Cytotoxic Lymphocytes Linked To Sleep Disturbances And Cognitive Decline In Early Alzheimer's Disease
Sophia Krix1,2,3, Neus Falgàs4,5, Sarah Hücker6, Andrea Val-Guardiola4, Agnès Pérez-Millán4,5, Anna Antonell4,5, Christina Stadler6, Judith Proske6, Stefan Kirsch6, Raquel Sánchez-Valle4,5, Kuti Baruch7, Holger Fröhlich1,2,3*
1) Department of Biomedical AI and Data Science, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, 53757 Sankt Augustin, Germany. 2) Bonn-Aachen International Center for Information Technology (b-it), University of Bonn, 53115 Bonn, Germany 3) Institute for Digital Medicine, University Hospital Bonn, Venusberg Campus 1, 53127 Bonn, Germany. 4) Alzheimer’s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, FRCB- Institutd’Investigació Biomedica August PiiSunyer (IDIBAPS), University of Barcelona, Barcelona, Spain 5) Centro de InvestigaciónBiomédicaen Red enEnfermedadesNeurodegenerativas (CIBERNED), Madrid, Spain. 6) Division of Personalized Tumor Therapy, Fraunhofer Institute for Toxicology and Experimental Medicine. ITEM, 93053 Regensburg, Germany.7) ImmunoBrain Ltd., 3 Haim Pekeris St., Rehovot 7670203, Israel.
Key Messages
Peripheral immune remodeling marks the transition from cognitive health -> mild cognitive impairment -> mild AD.
Immune-sleep-cognition axis: Peripheral immune changes are functionally linked to sleep and circadian disruptions.
T cell receptor repertoire contracts in mild cognitive impairment stage, and expands in mild AD.
Background
Alzheimer’s Disease (AD) often presents with early changes in sleep behavior and immune system dynamics long before cognitive decline is evident. Recognizing these early indicators is crucial for timely diagnosis and intervention.
Aim
Understand the interplay between changes in the immune system, developing sleep disturbances and cognitive decline.
Data: ADIS study
“Early Diagnosis of Alzheimer’s Disease by Immune Profiling of Cytotoxic Lymphocytes and Recording of Sleep Disturbances”
Duration: 07/2022 - 06/2025 | Funding: 1.3 Mio Euros by JPND Neurodegenerative Research
N= 79 participants
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Mild cognitive impairment (MCI)
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Alzheimer's Disease (AD)
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Healthy Controls (HC)
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Methods
Disentangling connectivity between data modalities
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Score-based, continuous structure learning
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Gradient-based optimization with differentiable constraints
Approach: Directed Acyclic Graphs vi M-matrices for Acyclicity (DAGMA) (Bello et al., 2022, Advances in Neural Information Processing Systems).
Exploring the complex relationships among cognition, sleep and peripheral immune system changes
Machine learning approaches for low-dimensional embedding of high-dimensional data
Results
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Natural Killer cells and CD8+ T effector memory cells show the most prominent stage-specific transcriptional dysregulation.
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Clustering analysis reveals differential expression in CD8 T effector memory cells and Natural Killer cell populations, including signs of cellular senescence.
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T cell receptor repertoire contraction in MCI, reshaping and expansion in AD, indicating reduced clonal diversity on the prodromal phase.
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Sleep-immune-cognition axis revealed through directed acyclic graph learning.
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