image: Figure 5. (A) Representative images and quantification of Aβ stained with thioflavin S in the hippocampus and cortex of 5xFAD mice treated with or without APC. (B) Radial arm water maze test showed the latencies to hidden platform and the errors happens in arms in WT and 5xFAD mice. N = 8, *p < 0.05, 5xFAD-Vehicle vs. WT-Vehicle; #p < 0.05, 5xFAD-APC vs. 5xFAD-Vehicle.
Credit: 2024 Fatmi et al.
“We believe our study utilizing Single-Cell RNA sequencing will provide additional rationale towards the effects on APC treatment observed in previous studies on 5xFAD AD mice.”
BUFFALO, NY- March 13, 2024 – A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 4, entitled, “Single-Cell RNA-seq reveals transcriptomic modulation of Alzheimer’s disease by activated protein C.”
Single-Cell RNA sequencing reveals changes in cell population in Alzheimer’s disease (AD) model 5xFAD (5x Familial AD mutation) versus wild type (WT) mice. In this new study, researchers Mohammad Kasim Fatmi, Hao Wang, Lily Slotabec, Changhong Wen, Blaise Seale, Bi Zhao, and Ji Li from the University of South Florida, University of Mississippi Medical Center and the G.V. (Sonny) Montgomery VA Medical Center used single-cell RNA sequencing and bioinformatic analysis to analyze the effects of APC [Activated Protein C] treatment on AD transgenic mice.
“In our investigation, we utilized transgenic mice that contain expression for five major amyloid pathologies that allow for rapid progression of AD and Aβ deposition known as 5xFAD mice.”
The returned sequencing data was processed through the 10x Genomics CellRanger platform to perform alignment and form corresponding matrix to perform bioinformatic analysis. Alterations in glial cells occurred in 5xFAD versus WT, especially increases in microglia proliferation were profound in 5xFAD. Differential expression testing of glial cells in 5xFAD versus WT revealed gene regulation. Globally, the critical genes implicated in AD progression are upregulated such as Apoe, Ctsb, Trem2, and Tyrobp.
Using this differential expression data, GO term enrichment was completed to observe possible biological processes impacted by AD progression. Utilizing anti-inflammatory and cyto-protective recombinant Activated Protein C (APC), the researchers uncovered inflammatory processes to be downregulated by APC treatment in addition to recuperation of nervous system processes. Moreover, animal studies demonstrated that administration of recombinant APC significantly attenuated Aβ burden and improved cognitive function of 5xFAD mice.
“The downregulation of highly expressed AD biomarkers in 5xFAD could provide insight into the mechanisms by which APC administration benefits AD.”
Read the full paper: DOI: https://doi.org/10.18632/aging.205624
Corresponding Authors: Bi Zhao, Ji Li
Corresponding Emails: bizhao@usf.edu, jli3@umc.edu
Keywords: APC, Alzheimer’s disease, inflammation
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About Aging:
Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.
Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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Journal
Aging-US
Method of Research
Experimental study
Subject of Research
Animals
Article Title
Single-Cell RNA-seq reveals transcriptomic modulation of Alzheimer’s disease by activated protein C
Article Publication Date
21-Feb-2024