Non-linear microglial, inflammatory and oligodendrocyte dynamics across stages of Alzheimer's disease

Article Article scientifique Article Non-linear microglial, inflammatory and oligodendrocyte dynamics across stages of Alzheimer's disease eng 2025-05-08 2025-07 author Badina Aurélien Matthieu Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 960813 Département de psychiatrie (PSYAT) author Ceyzeriat Kelly CIBM Center for Biomedical Imaging, Geneva, Switzerland. 910236 Centre d'imagerie bio-médicale (CIBM) author Amosse Quentin 0000-0002-5553-9594 Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland. 934939 author Tresch Alexandre Skander Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 923633 author Abjean Laurène Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland. 413354 Département de psychiatrie (PSYAT) author Guenat Léa Joanne Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 937282 author Vauthey Emilie Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 938602 author Tsartsalis Stergios 0000-0002-6565-6313 Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland. 782369 Département de psychiatrie (PSYAT) author Millet Philippe 0000-0002-5803-0478 Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland. 668343 Département de psychiatrie (PSYAT) author Tournier Benjamin Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland. Electronic address: Benjamin.tournier@unige.ch. 705309 Département de psychiatrie (PSYAT) 106950 10.1016/j.nbd.2025.106950 40348203 0969-9961 https://www.sciencedirect.com/science/article/pii/S0969996125001664 Alzheimer's disease (AD) is characterized by cognitive decline and neuropathological hallmarks including Aβ plaques and Tau tangles. Emerging evidence indicates oligodendrocyte (OL) dysfunction and demyelination also contribute to disease progression. Here, we analyzed OL markers and inflammatory gene expression in human hippocampal samples at early and late AD stages. In early AD, we observed OL and myelinating pathways downregulation, alongside microglial and astrocytic activation, as well as upregulated chemokine CCL2 and peripheral immune infiltration markers. In late stages, expression of OL-related genes and myelination pathways increase, with a higher NG2/MBP ratio, coinciding with decreased microglial coverage and peripheral immune markers. These findings indicate that early neuroinflammation may impair OL function, while attenuated immune activity in late AD allows partial OL recovery. This study provides insights into stage-specific inflammatory and myelin-related changes in AD, supporting the relevance of understanding oligodendrocyte dynamics and potential regenerative responses for future therapeutic strategies. Alzheimer's disease Microglia Myelination Neuroinflammation Oligodendrocytes Peripheral immune infiltration Dewey 616.89 Swiss National Science Foundation A translational assessment of central nervous system innate immunity to identify how social support and oxytocin interact to protect against Alzheimer’s disease 223414 CH Careers Swiss National Science Foundation TSPO in astrocytes and microglia: role and therapeutic potential in Alzheimer’s disease. 212322 CH Projects 60 Département de psychiatrie 225 false 1221 Neuroimagerie moléculaire en psychiatrie 983 https://yareta.unige.ch/archives/503146e9-05ea-46ff-952f-6c8740086b66 Neurobiology of disease 211 2aa83230-42bb-4c74-ad6a-1ca147399fdf Article (Published version) Public badina2025.pdf 10431564 application/pdf CC BY-4.0 319b89e603f865d96c13f3dcd204ad44d01adc5d9ea76077247bb5fe779d31c4 ec1ec1a9-c5a3-4b87-847e-710321447738 Supplemental data Public 1-s2.0-S0969996125001664-mmc1.pdf 2581428 application/pdf 72bd708d23c24dab5914ba1e8c71c81a16f87694e525d204024063565130c522 openAccess Faculté de médecine / Section de médecine clinique / Département de psychiatrie

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Non-linear microglial, inflammatory and oligodendrocyte dynamics across stages of Alzheimer's disease	Neurobiology of disease			2025	80	174

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Vauthey, Emilie