Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer's Disease

Norimichi Nakamura, Yasumasa Ohyagi, Tomohiro Imamura, Yuki T. Yanagihara, Kyoko M. Iinuma, Naoko Soejima, Hiroyuki Murai, Ryo Yamasaki, Jun Ichi Kira

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


Apomorphine (APO) promotes intraneuronal amyloid-β (Aβ) degradation and improves memory function in an Alzheimer's disease (AD) model, 3xTg-AD mice. Since insulin resistance is increased in AD neurons, we investigated the effects of APO on brain insulin resistance in 3xTg-AD mice at early and late stages. After 1-month subcutaneous injection of Apokyn® to 3xTg-AD mice at 6 or 12 months of age, memory function was significantly improved in both age groups. Protein levels of insulin-degrading enzyme (IDE), which is linked to insulin signaling and degrades Aβ, significantly increased in the 3xTg-AD mice brain compared with non-transgenic mice, and were further increased by APO. Protein levels of two types of serine-phosphorylated insulin receptor substrate-1 (IRS-1), pS616 and pS636/639, significantly decreased following APO treatment in the 13-month-old 3xTg-AD mice brain, suggesting improved brain insulin resistance. Immunostaining of the IDE, pS616 and pS636/639 IRS-1 demonstrated similar changes due to APO treatment. Thus, brain insulin resistance is considered an important therapeutic target in AD, and APO may provide improved neuronal insulin resistance.

Original languageEnglish
Pages (from-to)1151-1161
Number of pages11
JournalJournal of Alzheimer's Disease
Issue number4
Publication statusPublished - 2017

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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