Long-term treatment with lithium alleviates memory deficits and reduces amyloid-β production in an aged Alzheimer's disease transgenic mouse model

Xin Zhang, Xin Heng, Ting Li, Lixi Li, Dehua Yang, Xiaojie Zhang, Yunlan Du, Rachelle S. Doody, Weidong Le

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

The glycogen synthase kinase-3β (GSK3β) pathway plays a central role in Alzheimer's disease (AD) and its deregulation accounts for many of the pathological hallmarks of AD. Lithium, which modulates GSK3β activity, has been shown to reduce amyloid production and tau phosphorylation in pre-pathological AD mouse models. In this study, we investigated the effects of chronic LiCl treatment in aged double transgenic mice (AβPP Swe/PS1 A246E). We found that chronic lithium treatment decreased the γ-cleavage of amyloid-β protein precursor, further reduced amyloid-β production and senile plaque formation, accompanied by the improvement in spatial learning and memory abilities. Because autophagy may play an important role in the pathology of AD, we also assessed the autophagy activity and found that the chronic lithium treatment attenuated the autophagy activation in this AD mouse model. Our results suggest that prolonged lithium treatment, even during the later stages of AD, could be an effective therapeutics.

Original languageEnglish (US)
Pages (from-to)739-749
Number of pages11
JournalJournal of Alzheimer's Disease
Volume24
Issue number4
DOIs
StatePublished - 2011

Keywords

  • AβPP processing
  • Alzheimer's disease
  • autophagy
  • GSK3β
  • lithium chloriD.E.
  • spatial learning and memory

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

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