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Integrative Metabolomics and Whole Transcriptome Sequencing Reveal Role for TREM2 in Metabolism Homeostasis in Alzheimer's Disease

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机构： [1]Department of Neurology & Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing 100053, China [2]National Center for Neurological Disorders, 45 Changchun Street, Beijing 100053, China

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关键词： TREM2 Alzheimer’s disease Metabolome Transcriptome Integrative analysis Energy metabolism

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia worldwide. Dysregulation of various metabolism pathways may mediate the development of AD pathology and cognitive dysfunction. Variants of triggering receptor expressed on myeloid cells-2 (TREM2) are known to increase the risk of developing AD. TREM2 plays a role in AD development by maintaining cellular energy and biosynthesis, but the precise mechanism through which it accomplishes this is unknown. Metabolomic analysis of hippocampal tissue from APP/PS1 and APP/PS1-TREM2 knockout (KO) mice found that TREM2 KO was associated with abnormalities in several metabolism pathways, and the effect was particularly pronounced in lipid metabolism and glucose metabolism pathways. Consistently, transcriptomic analysis of these mice determined that most differentially expressed genes were involved in energy metabolism pathways. We screened seven differentially expressed genes in APP/PS1-TREM2 KO mice that may influence AD development by altering energy metabolism. Integrative analysis of the metabolomic and transcriptomic profiles showed that TREM2 may regulate lipid metabolism and sphingolipid metabolism by affecting lipoprotein lipase (LPL) expression, thereby influencing AD progression. Our results prompt further studies of the interactions among TREM2, LPL, glucolipid metabolism, and sphingolipid metabolism in AD to identify new diagnostic and treatment strategies.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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出版当年[2022]版：

大类 | 2 区医学

小类 | 2 区神经科学

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大类 | 2 区医学

小类 | 2 区神经科学

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Q2 NEUROSCIENCES

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Q1 NEUROSCIENCES

影响因子： 4.6 最新[2023版] 4.7 最新五年平均 5.686 出版当年[2021版] 5.576 出版当年五年平均 5.59 出版前一年[2020版] 5.1 出版后一年[2022版]

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第一作者机构： [1]Department of Neurology & Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing 100053, China

通讯作者：

通讯机构： [1]Department of Neurology & Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing 100053, China [2]National Center for Neurological Disorders, 45 Changchun Street, Beijing 100053, China

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