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

IF 5.1 2区医学 Q1 NEUROSCIENCES

Neurobiology of Disease Pub Date : 2025-05-08 DOI:10.1016/j.nbd.2025.106950

Aurélien M. Badina , Kelly Ceyzériat , Quentin Amossé , Alexandre Tresh , Laurene Abjean , Léa Guénat , Emilie Vauthey , Stergios Tsartsalis , Philippe Millet , Benjamin B. Tournier

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Abstract

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.

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阿尔茨海默病各阶段的非线性小胶质细胞、炎症和少突胶质细胞动力学

阿尔茨海默病（AD）的特点是认知能力下降和神经病理标志，包括β斑块和Tau缠结。新出现的证据表明，少突胶质细胞（OL）功能障碍和脱髓鞘也有助于疾病进展。在这里，我们分析了阿尔茨海默病早期和晚期人类海马样本中的OL标记物和炎症基因表达。在早期AD中，我们观察到OL和髓鞘通路下调，同时小胶质细胞和星形胶质细胞活化，趋化因子CCL2和外周免疫浸润标志物上调。在晚期，ol相关基因和髓鞘通路的表达增加，NG2/MBP比值升高，与小胶质细胞覆盖率和外周免疫标记物下降相一致。这些发现表明，早期神经炎症可能损害OL功能，而阿尔茨海默病晚期免疫活性减弱可使OL部分恢复。这项研究为阿尔茨海默病的分期特异性炎症和髓磷脂相关变化提供了见解，支持理解少突胶质细胞动力学和潜在再生反应与未来治疗策略的相关性。

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来源期刊

Neurobiology of Disease 医学-神经科学

CiteScore

11.20

自引率

3.30%

发文量

270

审稿时长

76 days

期刊介绍： Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.