Swedish amyloid precursor protein mutation increases cell cycle-related proteins in vitro and in vivo

Kwang Woo Ahn, Yuyoung Joo, Yoori Choi, Minji Kim, Sang Hyoung Lee, Seok Ho Cha, Yoo Hun Suh, Hye Sun Kim

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Reactivation of the cell cycle, including DNA replication, might play a major role in Alzheimer's disease. In this study, we report that the expressions of Swedish double mutation of amyloid precursor protein (Swe-APP) or of the APP intracellular domain (AICD) into nerve growth factor (NGF)-differentiated PC12 cells or rat primary cortical neurons increased mRNA and protein levels of cyclin D1 and cyclin B1. Treatment with lithium chloride (a glycogen synthase kinase-3β inhibitor) down-regulated cyclin B1 induced by Swe-APP expression but up-regulated cyclin D1 expression induced by Swe-APP, suggesting that glycogen synthase kinase-32b activity is involved in these expression changes of cyclins D1 and B1. Swe-APP, which is a prevailing cause of familial Alzheimer's disease, is well known to increase amyloid beta peptide production both in vitro and in vivo, but the underlying molecular means whereby it leads to the pathogenesis of AD remains unknown. The finding that cyclin D1 and B1 expressions were up-regulated by Swe-APP in in vitro cultured cells was substantiated in the brain tissues of Tg2576 mice, which harbor the Swe-APP mutation. These results suggest that some disturbances in cell cycle regulation may be involved in Swe-APP or AICD-induced neurodegeneration and that these contribute to the pathogenesis of AD.

Original languageEnglish
Pages (from-to)2476-2487
Number of pages12
JournalJournal of Neuroscience Research
Issue number11
StatePublished - 15 Aug 2008


  • Alzheimer's disease
  • Cell cycle
  • Cyclin B1
  • Cyclin D1
  • Neurodegeneration
  • Swedish amyloid precursor protein

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