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Cells
Volume 14
Issue 4
10.3390/cells14040250
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Article

Peripheral Immune Profiles in Individuals at Genetic Risk of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease

by
Laura Deecke
1,
Olena Ohlei
1,
David Goldeck
2,
Jan Homann
1,
Sarah Toepfer
3,
Ilja Demuth
3,4,
Lars Bertram
5,
Graham Pawelec
2,6 and
Christina M. Lill
1,7,*
1
Institute of Epidemiology and Social Medicine, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany
2
Department of Immunology, University of Tübingen, 72076 Tübingen, Germany
3
Department of Endocrinology and Metabolic Diseases (Including Division of Lipid Metabolism), Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
4
BCRT—Berlin Institute of Health Center for Regenerative Therapies, Berlin Institute of Health, Charité—Universitätsmedizin Berlin, 10117 Berlin, Germany
5
Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, 23562 Lübeck, Germany
6
Health Sciences North Research Institute of Canada, Sudbury, ON P3E 2H3, Canada
7
Ageing and Epidemiology Unit (AGE), School of Public Health, Imperial College London, London W6 8RP, UK
*
Author to whom correspondence should be addressed.
Cells 2025, 14(4), 250; https://doi.org/10.3390/cells14040250
Submission received: 20 December 2024 / Revised: 23 January 2025 / Accepted: 4 February 2025 / Published: 10 February 2025
(This article belongs to the Special Issue New Advances in Neuroinflammation)
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Abstract

The immune system plays a crucial role in the pathogenesis of neurodegenerative diseases. Here, we explored whether blood immune cell profiles are already altered in healthy individuals with a genetic predisposition to amyotrophic lateral sclerosis (ALS) or Alzheimer’s disease (AD). Using multicolor flow cytometry, we analyzed 92 immune cell phenotypes in the blood of 448 healthy participants from the Berlin Aging Study II. We calculated polygenic risk scores (PGSs) using genome-wide significant SNPs from recent large genome-wide association studies on ALS and AD. Linear regression analyses were then performed of the immune cell types on the PGSs in both the overall sample and a subgroup of older participants (>60 years). While we did not find any significant associations between immune cell subtypes and ALS and AD PGSs when controlling for the false discovery rate (FDR = 0.05), we observed several nominally significant results (p < 0.05) with consistent effect directions across strata. The strongest association was observed with CD57+ CD8+ early-memory T cells and ALS risk (p = 0.006). Other immune cell subtypes associated with ALS risk included PD-1+ CD8+ and CD57+ CD4+ early-memory T cells, non-classical monocytes, and myeloid dendritic cells. For AD, naïve CD57+ CD8+ T cells and mature NKG2A+ natural killer cells showed nominally significant associations. We did not observe major immune cell changes in individuals at high genetic risk of ALS or AD, suggesting they may arise later in disease progression. Additional studies are required to validate our nominally significant findings.
Keywords: immune system; immune cell; neurodegeneration; polygenic risk score; disease prediction immune system; immune cell; neurodegeneration; polygenic risk score; disease prediction

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MDPI and ACS Style

Deecke, L.; Ohlei, O.; Goldeck, D.; Homann, J.; Toepfer, S.; Demuth, I.; Bertram, L.; Pawelec, G.; Lill, C.M. Peripheral Immune Profiles in Individuals at Genetic Risk of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease. Cells 2025, 14, 250. https://doi.org/10.3390/cells14040250

AMA Style

Deecke L, Ohlei O, Goldeck D, Homann J, Toepfer S, Demuth I, Bertram L, Pawelec G, Lill CM. Peripheral Immune Profiles in Individuals at Genetic Risk of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease. Cells. 2025; 14(4):250. https://doi.org/10.3390/cells14040250

Chicago/Turabian Style

Deecke, Laura, Olena Ohlei, David Goldeck, Jan Homann, Sarah Toepfer, Ilja Demuth, Lars Bertram, Graham Pawelec, and Christina M. Lill. 2025. "Peripheral Immune Profiles in Individuals at Genetic Risk of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease" Cells 14, no. 4: 250. https://doi.org/10.3390/cells14040250

APA Style

Deecke, L., Ohlei, O., Goldeck, D., Homann, J., Toepfer, S., Demuth, I., Bertram, L., Pawelec, G., & Lill, C. M. (2025). Peripheral Immune Profiles in Individuals at Genetic Risk of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease. Cells, 14(4), 250. https://doi.org/10.3390/cells14040250

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