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<p>Alzheimer’s disease (AD), a major neurodegenerative disorder, lacks effective early diagnostic and therapeutic strategies. This study aimed to investigate the diagnostic utility of Long non-coding RNAs HLA Complex Group 18 ( HCG18) in AD and elucidate its molecular mechanisms in neuronal injury.&#xa0;Eighty-three AD patients and 83 healthy controls (HC) were enrolled. Serum samples were analyzed for HCG18 expression using qRT-PCR and cerebrospinal fluid (CSF) samples were analyzed for AD biomarkers by ELISA. Diagnostic performance was assessed using ROC analysis. Aβ1-42-treated HT22 cells (Immortalized murine hippocampal neuronal-like cell line) were employed to model neuronal injury, with HCG18 knockdown and miR-425-3p inhibition experiments conducted to validate functional interactions. HT22 cell apoptosis, oxidative stress markers (SOD, GSH-Px, MDA, ROS), and HCG18/miR-425-3p interactions were evaluated through flow cytometry, biochemical assays, and dual-luciferase reporter systems.&#xa0;Serum HCG18 levels were significantly elevated in AD patients compared to HC (<i>P</i> &lt; 0.001), exhibiting strong diagnostic accuracy (AUC = 0.889). HCG18 expression correlated negatively with CSF Aβ1–42 (<i>r</i>=-0.709) and MMSE scores (<i>r</i>=-0.657), but positively with t-tau (<i>r</i> = 0.591) and p-tau181 (<i>r</i> = 0.582). In Aβ1-42-treated HT22 cells, HCG18 knockdown reduced apoptosis, suppressed ROS, and normalized oxidative stress markers. Mechanistically, HCG18 directly bound to and acted as a molecular sponge for miR-425-3p, sequestering its function; the downregulation of miR-425-3p mediated by a synthetic inhibitor reversed the protective effects of HCG18 silencing.&#xa0;HCG18 serves as a potential non-invasive biomarker for AD, exacerbating neuronal injury via sponging miR-425-3p to disrupt redox balance. Targeting the HCG18/miR-425-3p axis may offer new therapeutic strategies for AD.</p>

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HCG18 is a Potential Pathogenic Factor and Diagnostic Biomarker Alzheimer’s Disease

  • 期刊论文

  • 发表日期：

    2026年2月7日

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  • Pingting Chen,
  • Genru Li,
  • Lingyan Cheng,
  • Yumei Liu,
  • Yan Liu

摘要

Alzheimer’s disease (AD), a major neurodegenerative disorder, lacks effective early diagnostic and therapeutic strategies. This study aimed to investigate the diagnostic utility of Long non-coding RNAs HLA Complex Group 18 ( HCG18) in AD and elucidate its molecular mechanisms in neuronal injury. Eighty-three AD patients and 83 healthy controls (HC) were enrolled. Serum samples were analyzed for HCG18 expression using qRT-PCR and cerebrospinal fluid (CSF) samples were analyzed for AD biomarkers by ELISA. Diagnostic performance was assessed using ROC analysis. Aβ1-42-treated HT22 cells (Immortalized murine hippocampal neuronal-like cell line) were employed to model neuronal injury, with HCG18 knockdown and miR-425-3p inhibition experiments conducted to validate functional interactions. HT22 cell apoptosis, oxidative stress markers (SOD, GSH-Px, MDA, ROS), and HCG18/miR-425-3p interactions were evaluated through flow cytometry, biochemical assays, and dual-luciferase reporter systems. Serum HCG18 levels were significantly elevated in AD patients compared to HC (P < 0.001), exhibiting strong diagnostic accuracy (AUC = 0.889). HCG18 expression correlated negatively with CSF Aβ1–42 (r=-0.709) and MMSE scores (r=-0.657), but positively with t-tau (r = 0.591) and p-tau181 (r = 0.582). In Aβ1-42-treated HT22 cells, HCG18 knockdown reduced apoptosis, suppressed ROS, and normalized oxidative stress markers. Mechanistically, HCG18 directly bound to and acted as a molecular sponge for miR-425-3p, sequestering its function; the downregulation of miR-425-3p mediated by a synthetic inhibitor reversed the protective effects of HCG18 silencing. HCG18 serves as a potential non-invasive biomarker for AD, exacerbating neuronal injury via sponging miR-425-3p to disrupt redox balance. Targeting the HCG18/miR-425-3p axis may offer new therapeutic strategies for AD.