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July 18th, 2025
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SUNY Upstate Medical University
neuroscience
biorxiv

Transcriptomic analysis reveals new reparative mechanisms of SCF and GCSF - reduced neuropathology in aged APPPS1 mice

Addo, A.Open in Google Scholar•Li, B.Open in Google Scholar•Murikinati, S.Open in Google Scholar•Gardner, R.Open in Google Scholar•Zhao, L.-R.Open in Google Scholar

Alzheimers 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, GCSF, reduces AD pathology in APPPS1 mice. This study aimed to explore the molecular mechanism underlying SCF and GCSF therapeutic effects using transcriptomic analysis. Aged APPPS1 mice received daily subcutaneous injections of SCF and GCSF 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 {middle dot} 0, Reactome, and ShinyGO 0 {middle dot} 77. A total of 45037 differentially expressed genes, DEGs, were detected. Twenty {middle dot} seven DEGs met a[≥] 2 - fold threshold in SCF and GCSF - treated versus vehicle - treated APPPS1 mice, 89 DEGs met this threshold in APPPS1 versus WT mice. SCF and GCSF 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 and GCSF downregulated several oncogenes, including Cbl, Akap9, Kcnq1ot1, and Snhg11, highlighting an overlap between cancer and AD - related pathways. SCF and GCSF 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 and GCSF treatment modifies immune and metabolic pathways, reduces AD pathology, and highlights new therapeutic targets involving inflammation, metal homeostasis, and oncogenic signaling.

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