ArticleActa neuropathologica2024
Elevated expression of the retrotransposon LINE-1 drives Alzheimer's disease-associated microglial dysfunction.
Article in Acta neuropathologica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- A Standardized Protocol for Generating iPSC-Derived Human Microglia for Functional Genomic Assays.Methods in molecular biology (Clifton, N.J.) · 2027Article
- The therapeutic potential of transposable element activity modulation.EMBO molecular medicine · 2026Review
- Targeting innovative therapeutic approaches to the hallmarks of aging to combat Alzheimer's disease.Neural regeneration research · 2026Article
- AcutebioRxiv : the preprint server for biology · 2026Article
- Transposable element regulation in mammalian germ cells and other contexts: multilayered repression, fertility, and regulated activation.Epigenomics · 2026Review
- Review
- Viral Mimicry of Alzheimer's Disease: Innate Sensing of Self-Nucleic Acids as a Driver of Glial Senescence.Journal of molecular neuroscience : MN · 2026Review
- Literature-derived serum miRNA signatures associated with cognitive decline in Alzheimer's disease: integrated analysis and machine learning-based diagnostic modeling.Alzheimer's research & therapy · 2026Article
- Plasma EV LINE-1 mRNA as a diagnostic biomarker for differentiating Alzheimer's disease from non-Alzheimer's dementias.Alzheimer's research & therapy · 2026Article
- Role of Microglial Dysfunction in Parkinson's Disease: From Multifactorial Causes to Neurodegeneration.Neuroscience bulletin · 2026Review
- The Role of Non-LTR Retrotransposons in Sterile Inflammation: Mechanisms and Therapeutic Potential.Biomedicines · 2026Review
- Role of LINE-1 in the nervous system and neurological disorders.Chinese medical journal · 2026Review
- Systemic LINE-1 RNA in Plasma Extracellular Vesicles Drives Neuroinflammation and Cognitive Dysfunction via cGAS-STING Pathway in Aging.Aging cell · 2026Article
- The APOE4-estrogen-microglia axis in perimenopausal cognitive changes: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
- Article
- Unveiling Aging and Alzheimer's Disease-Associated Dynamics of LINE1 DNA Content and Protein Expression in Mouse Brains.Aging cell · 2025Article
- Retrotransposon Protein L1 ORF1p Expression in Aging Central Nervous System.International journal of molecular sciences · 2025Article
- Edge of RNA m6A modification on LINE-1 retrotransposons in central nervous system: merely a transcriptional control?Epigenomics · 2025Article
- Cellular insights into transposable elements in Alzheimer's disease.Frontiers in molecular biosciences · 2025Article
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Authors and funding
8 authors.
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Abstract
Aberrant activity of the retrotransposable element long interspersed nuclear element-1 (LINE-1) has been hypothesized to contribute to cellular dysfunction in age-related disorders, including late-onset Alzheimer's disease (LOAD). However, whether LINE-1 is differentially expressed in cell types of the LOAD brain, and whether these changes contribute to disease pathology is largely unknown. Here, we examined patterns of LINE-1 expression across neurons, astrocytes, oligodendrocytes, and microglia in human postmortem prefrontal cortex tissue from LOAD patients and cognitively normal, age-matched controls. We report elevated immunoreactivity of the open reading frame 1 protein (ORF1p) encoded by LINE-1 in microglia from LOAD patients and find that this immunoreactivity correlates positively with disease-associated microglial morphology. In human iPSC-derived microglia (iMG), we found that CRISPR-mediated transcriptional activation of LINE-1 drives changes in microglial morphology and cytokine secretion and impairs the phagocytosis of amyloid beta (Aβ). We also find LINE-1 upregulation in iMG induces transcriptomic changes genes associated with antigen presentation and lipid metabolism as well as impacting the expression of many AD-relevant genes. Our data posit that heightened LINE-1 expression may trigger microglial dysregulation in LOAD and that these changes may contribute to disease pathogenesis, suggesting a central role for LINE-1 activity in human LOAD.
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