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<p>We previously demonstrated that ibrutinib has therapeutic efficacy against AD pathologies when injected intraperitoneally at a lower dosage (10&#xa0;mg/kg, daily for 2 weeks) or orally at a higher dosage (30&#xa0;mg/kg, daily for 1 month) in AD mice models. However, the effect of chronic lower dose of ibrutinib by oral administration on AD pathologies has not been investigated yet. Therefore, we investigated whether long-term oral administration of ibrutinib at a lower dose (1 or 10&#xa0;mg/kg, daily for 5 months) on AD pathology and in vivo toxicity in 5xFAD mice. We found ibrutinib enhanced cognitive function and alleviated Aβ pathology in 5xFAD mice without hepatotoxicity. Furthermore, ibrutinib-treated 5xFAD mice decrease tau hyperphosphorylation, p-GSK3α/β levels, and markers of neuroinflammation such as Iba-1, GFAP, and NLRP3. Collectively, these translational studies indicate chronic oral administration of ibrutinib at low doses improves cognitive function and suppresses AD pathology/neuroinflammation in an AD mice model thereby having potential as an effective multitarget AD therapeutic in clinical application.</p>

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Chronic oral administration of ibrutinib prevents long-term memory deficits and reduces AD pathology and neuroinflammatory responses in a mouse model of AD

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月21日

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  • Hyun-ju Lee,
  • Sora Kang,
  • Yoo Joo Jeong,
  • Jin-Hee Park,
  • Jeong-Woo Hwang,
  • Chan-Hu Gu,
  • Tae-Mi Jung,
  • Seokjun Oh,
  • Ji-Yeong Jang,
  • Hyang-Sook Hoe

摘要

We previously demonstrated that ibrutinib has therapeutic efficacy against AD pathologies when injected intraperitoneally at a lower dosage (10 mg/kg, daily for 2 weeks) or orally at a higher dosage (30 mg/kg, daily for 1 month) in AD mice models. However, the effect of chronic lower dose of ibrutinib by oral administration on AD pathologies has not been investigated yet. Therefore, we investigated whether long-term oral administration of ibrutinib at a lower dose (1 or 10 mg/kg, daily for 5 months) on AD pathology and in vivo toxicity in 5xFAD mice. We found ibrutinib enhanced cognitive function and alleviated Aβ pathology in 5xFAD mice without hepatotoxicity. Furthermore, ibrutinib-treated 5xFAD mice decrease tau hyperphosphorylation, p-GSK3α/β levels, and markers of neuroinflammation such as Iba-1, GFAP, and NLRP3. Collectively, these translational studies indicate chronic oral administration of ibrutinib at low doses improves cognitive function and suppresses AD pathology/neuroinflammation in an AD mice model thereby having potential as an effective multitarget AD therapeutic in clinical application.