Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Here we elucidate the effect of Alzheimer disease (AD)-predisposing genetic backgrounds, APOE4, PSEN1ΔE9, and APPswe, on functionality of human microglia-like cells (iMGLs). We present a physiologically relevant high-yield protocol for producing iMGLs from induced pluripotent stem cells. Differentiation is directed with small molecules through primitive erythromyeloid progenitors to re-create microglial ontogeny from yolk sac. The iMGLs express microglial signature genes and respond to ADP with intracellular Ca release distinguishing them from macrophages. Using 16 iPSC lines from healthy donors, AD patients and isogenic controls, we reveal that the APOE4 genotype has a profound impact on several aspects of microglial functionality, whereas PSEN1ΔE9 and APPswe mutations trigger minor alterations. The APOE4 genotype impairs phagocytosis, migration, and metabolic activity of iMGLs but exacerbates their cytokine secretion. This indicates that APOE4 iMGLs are fundamentally unable to mount normal microglial functionality in AD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829767 | PMC |
| http://dx.doi.org/10.1016/j.stemcr.2019.08.004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Thionine modulates tau phosphorylation in an Alzheimer's disease cell culture model.
Turk J Biol
June 2025
Department of Biochemistry, School of Pharmacy, Hacettepe University, Ankara, Turkiye.
Background/aim: Tau protein, which is crucial for sustaining the cytoskeletal network by assisting microtubule construction, contributes significantly to the pathophysiology of Alzheimer's disease (AD). The hyperphosphorylation of tau causes it to detach from microtubules (MTs), leading to the formation of neurofibrillary tangles (NFTs) in neurons, which ultimately results in cell death. Thionine (TH), a cationic phenothiazine-structured compound, has been the topic of extensive research due to its interesting physicochemical properties.
View Article and Find Full Text PDFNesfatin-1 ameliorates blood-brain barrier dysfunction in Alzheimer's disease by targeting VEGF-R1 and reducing cellular senescence in brain vascular endothelial cells.
Transl Psychiatry
September 2025
Department of Geriatric Medicine, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 518107, China.
Cellular senescence and associated endothelial permeability are crucial factors in the dysfunction of the blood-brain barrier (BBB) in neurodegenerative diseases, including Alzheimer's disease (AD). Nesfatin-1 (NF-1), a neuropeptide involved in regulating appetite and energy homeostasis, has not been extensively studied for its pathophysiological role in AD. In this study, we found that NF-1 treatment improved cellular senescence in brain vascular endothelial bEnd.
View Article and Find Full Text PDFAntigen-Specifically Activated CD8+ and Double-Negative T Cells Accumulate in the Brain of Alzheimer's Disease Mice.
Aging Dis
August 2025
Department of Neurology, University Medicine, 17475 Greifswald, Germany.
Emerging evidence suggests adaptive immunity plays a key role in cognitive function and neurodegenerative diseases. However, the specific contribution of T cells in Alzheimer's disease (AD) remains poorly understood. Despite successful T cell modulation in other neurological conditions, similar strategies in AD remain underexplored due to gaps in our understanding of antigen-specific T cell activity and antigen-unspecific bystander activation in the diseased brain.
View Article and Find Full Text PDFFerulic acid derived from Huanshaodan improves cognitive deficits in Alzheimer's disease model through regulating APP proteolytic processing via downregulation of SIRT2 expression.
J Ethnopharmacol
August 2025
Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Collaborative Innovation Center of Prevention and Treatment of Major Diseases By Chinese and Western Medicine, Henan Province, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine,
Ethnopharmacological Relevance: Huanshaodan (HSD) is a Traditional Chinese Medicine Compound Prescription, traditionally used in the clinical treatment of Alzheimer's disease (AD) in China. Nevertheless, its bioactive constituents and mechanistic basis remain poorly understood.
Aim Of The Study: To identify the components derived from HSD that inhibit SIRT2 and investigate the underlying mechanisms in mitigating AD pathogenesis.
Therapeutic Effects of Neuro-Cells on Amyloid Pathology, BDNF Levels, and Insulin Signalling in APPswe/PSd1E9 Mice.
Cells
August 2025
Department of Psychiatry and Neuropsychology, Maastricht University, 6229 ER Maastricht, The Netherlands.
Stem cell therapies, including mesenchymal (MSCs) and haematopoietic stem cells (HSCs), have shown promise in neurodegenerative diseases. Here, we investigated the therapeutic effects of a defined combination of unmanipulated MSCs and CD34 HSCs, termed Neuro-Cells (NC), in a murine model of Alzheimer's disease (AD), the APPswe/PS1dE9 mouse. At 12 months of age, mice received intracisternal injections of NC (1.
View Article and Find Full Text PDF