Peripheral Immune Profiles in Individuals at Genetic Risk of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease
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...
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2025-02-01
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| author | Laura Deecke Olena Ohlei David Goldeck Jan Homann Sarah Toepfer Ilja Demuth Lars Bertram Graham Pawelec Christina M. Lill |
| author_facet | Laura Deecke Olena Ohlei David Goldeck Jan Homann Sarah Toepfer Ilja Demuth Lars Bertram Graham Pawelec Christina M. Lill |
| author_sort | Laura Deecke |
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| description | 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 (<i>p</i> < 0.05) with consistent effect directions across strata. The strongest association was observed with CD57+ CD8+ early-memory T cells and ALS risk (<i>p</i> = 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. |
| format | Article |
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| institution | DOAJ |
| issn | 2073-4409 |
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| publishDate | 2025-02-01 |
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| spelling | doaj-art-b714bdeee8ac4f8da663df34efaee3052025-08-20T02:44:59ZengMDPI AGCells2073-44092025-02-0114425010.3390/cells14040250Peripheral Immune Profiles in Individuals at Genetic Risk of Amyotrophic Lateral Sclerosis and Alzheimer’s DiseaseLaura Deecke0Olena Ohlei1David Goldeck2Jan Homann3Sarah Toepfer4Ilja Demuth5Lars Bertram6Graham Pawelec7Christina M. Lill8Institute of Epidemiology and Social Medicine, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, GermanyInstitute of Epidemiology and Social Medicine, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, GermanyDepartment of Immunology, University of Tübingen, 72076 Tübingen, GermanyInstitute of Epidemiology and Social Medicine, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, GermanyDepartment 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, GermanyDepartment 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, GermanyLübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, 23562 Lübeck, GermanyDepartment of Immunology, University of Tübingen, 72076 Tübingen, GermanyInstitute of Epidemiology and Social Medicine, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, GermanyThe 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 (<i>p</i> < 0.05) with consistent effect directions across strata. The strongest association was observed with CD57+ CD8+ early-memory T cells and ALS risk (<i>p</i> = 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.https://www.mdpi.com/2073-4409/14/4/250immune systemimmune cellneurodegenerationpolygenic risk scoredisease prediction |
| spellingShingle | Laura Deecke Olena Ohlei David Goldeck Jan Homann Sarah Toepfer Ilja Demuth Lars Bertram Graham Pawelec Christina M. Lill Peripheral Immune Profiles in Individuals at Genetic Risk of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease Cells immune system immune cell neurodegeneration polygenic risk score disease prediction |
| title | Peripheral Immune Profiles in Individuals at Genetic Risk of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease |
| title_full | Peripheral Immune Profiles in Individuals at Genetic Risk of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease |
| title_fullStr | Peripheral Immune Profiles in Individuals at Genetic Risk of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease |
| title_full_unstemmed | Peripheral Immune Profiles in Individuals at Genetic Risk of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease |
| title_short | Peripheral Immune Profiles in Individuals at Genetic Risk of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease |
| title_sort | peripheral immune profiles in individuals at genetic risk of amyotrophic lateral sclerosis and alzheimer s disease |
| topic | immune system immune cell neurodegeneration polygenic risk score disease prediction |
| url | https://www.mdpi.com/2073-4409/14/4/250 |
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