ArticleJournal of cellular physiology2024
Gender differences in Alzheimer's may be associated with TLR4-LYN expression in damage associated microglia and neuronal phagocytosis.
Article in Journal of cellular physiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Article
- Toll like receptor 4 (TLR4) in neuroinflammation: From acute hemorrhagic stroke to chronic neurodegeneration.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Immune-Enhancement Effects of 6-Methoxykaempferol on Cyclophosphamide-Induced Immunosuppression via Improving Antioxidant Enzyme Expression, NF-κB and MAPK Signaling, and Modulating Gut Microbiome.Antioxidants (Basel, Switzerland) · 2026Article
- Taking its TOLL: the role of toll-like receptor 4 in human health and disease, and its potential as a therapeutic target.Frontiers in immunology · 2026Review
- Consideration of sex as a biological variable over the history of the 5xFAD Alzheimer's Disease mouse model.Biology of sex differences · 2025Article
- Development of a 3D Brain Model to Study Sex-Specific Neuroinflammation After Hemorrhagic Stroke.Translational stroke research · 2025Article
- Microglial TLR4-Lyn kinase is a critical regulator of neuroinflammation, Aβ phagocytosis, neuronal damage, and cell survival in Alzheimer's disease.Scientific reports · 2025Article
- Sex Dependent Disparities in the Central Innate Immune Response after Moderate Spinal Cord Contusion in Rat.Cells · 2024Article
- Genetic and Epigenetic Sexual Dimorphism of Brain Cells during Aging.Brain sciences · 2023Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The role of Aβ plaques and neurofibrillary tangles in Alzheimer's disease (AD) pathogenesis have recently come into question due to failure of many pharmaceutical agents targeting these deposits and detection of these misfolded proteins in normal human brains. Therefore, we investigated correlations between microglial activation and toll like receptor 4 (TLR4) and Lck/Yes novel tyrosine (LYN) kinase signaling in an AD mouse model. In this study, we used 5-6-month-old 5XFAD and wild type (WT) male and female mice. Immunohistochemistry (IHC) and flow cytometry (FC) were performed on their brains. Cognitive performance was assessed with the Barnes-Maze. IHC showed more Ab aggregation in microglia of female 5XFAD mice compared to their male counterparts. Increased co-localization of microglial TLR4 and LYN was also observed in AD more than WT and females more than males. IHC also suggests microglial phagocytosis of neurons in AD mice, which is supported by FC data. Our FC data also support the involvement of disease associated microglia (DAMs) in this process based on cytokine secretion. Cognitive assessment by the Barnes maze showed 5XFAD females performed worse than males. In this study, we investigated the relationship between microglial TLR4 and LYN kinase in 5XFAD male and females. Our data reveals a correlation between microglial TLR4 and LYN co-localization and AD pathogenesis, more in females than males. Targeting microglial TLR4 and Lyn in DAMs may offer new therapeutic opportunities in the treatment of AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.