Work

Transcriptomic analysis identifies candidate molecular mechanisms underlying SCF+G-CSF-reduced neuropathology in aged APP/PS1 mice

Year: 2026

Type: article

Abstract: Alzheimer’s Disease (AD) is a neurodegenerative disease characterized by amyloid plaque deposition, tau hyperphosphorylation, neuroinflammation, and cognitive decline. Our previous studies showed that combined treatment with stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) reduces AD pathology in APP/PS1 mice. This study aimed to explore the molecular mechanism underlying SCF+G-CSF’s therapeutic effects using transcriptomic analysis. Aged APP/PS1 mice received daily subcutaneous injections of SCF+G-CSF or vehicle for 12 days. RNA was extracted from brain tissue on day 13 for gene chip analysis. Age-matched wild-type (WT) mice served as controls. Data were analyzed using TAC, STRING v12.0, Reactome, and ShinyGO 0.77. A total of 45,037 differentially expressed genes (DEGs) were detected. Twenty-seven DEGs met a ≥2-fold threshold in SCF+G-CSF-treated vs. vehicle-treated APP/PS1 mice; 89 DEGs met this threshold in APP/PS1 vs. WT mice. SCF+G-CSF treatment upregulated six immune-related genes (S100a8, S100a9, Ngp, Lcn2, Ltf, and Camp) associated with amyloid clearance, immune cell recruitment, and repair. Pathway analysis showed downregulation of IL-2, IL-4, IL-7, and EGFR1, and upregulation of IL-17 signaling, suggesting modulation of both innate and adaptive immunity. Notably, SCF+G-CSF downregulated several oncogenes, including Cbl, Akap9, Kcnq1ot1, and Snhg11, highlighting an overlap between cancer and AD-related pathways. SCF+G-CSF also promoted NADPH oxidase activation via Rho GTPases and showed >400-fold enrichment in metal ion sequestration, indicating potential metal chelation effects. These findings suggest that SCF+G-CSF treatment modifies immune and metabolic pathways, reduces AD pathology, and highlights new therapeutic targets involving inflammation, metal homeostasis, and oncogenic signaling.

Source: Frontiers in Aging Neuroscience

DOI: 10.3389/fnagi.2026.1705436

Authors: Afua Addo, Bin Li, Sasidhar Murikinati, Robert Gardner, Li-Ru Zhao

Institutions: SUNY Upstate Medical University, Louisiana State University Health Sciences Center Shreveport

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801