Retinoic acid attenuates β-amyloid deposition and rescues memory deficits in an Alzheimer's disease transgenic mouse model

Yun Ding, Aimin Qiao, Ziqing Wang, J. Shawn Goodwin, Eun Sook Lee, Michelle L. Block, Matthew Allsbrook, Michael Mcdonald, Guo Huang Fan

Research output: Contribution to journalArticle

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Abstract

Recent studies have revealed that disruption of vitamin A signaling observed in Alzheimer's disease (AD) leads to β-amyloid (Aβ) accumulation and memory deficits in rodents. The aim of the present study was to evaluate the therapeutic effect of all-trans retinoic acid (ATRA), an active metabolite of vitamin A, on the neuropathology and deficits of spatial learning and memory in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic mice, a well established AD mouse model. Here we report a robust decrease in brain Aβ deposition and tau phosphorylation in the blinded study of APP/PS1 transgenic mice treated intraperitoneally for 8 weeks with ATRA (20 mg/kg, three times weekly, initiated when the mice were 5 months old). This was accompanied by a significant decrease in the APP phosphorylation and processing. The activity of cyclin-dependent kinase 5, a major kinase involved in both APP and tau phosphorylation, was markedly downregulated by ATRA treatment. The ATRA-treated APP/PS1 mice showed decreased activation of microglia and astrocytes, attenuated neuronal degeneration, and improved spatial learning and memory compared with the vehicle-treated APP/PS1 mice. These results support ATRA as an effective therapeutic agent for the prevention and treatment of AD.

Original languageEnglish (US)
Pages (from-to)11622-11634
Number of pages13
JournalJournal of Neuroscience
Volume28
Issue number45
DOIs
StatePublished - Nov 5 2008

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Amyloid beta-Protein Precursor
Memory Disorders
Tretinoin
Amyloid
Transgenic Mice
Alzheimer Disease
Presenilin-1
Phosphorylation
Vitamin A
Cyclin-Dependent Kinase 5
Microglia
Therapeutic Uses
Astrocytes
Rodentia
Phosphotransferases
Down-Regulation
Brain

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Retinoic acid attenuates β-amyloid deposition and rescues memory deficits in an Alzheimer's disease transgenic mouse model. / Ding, Yun; Qiao, Aimin; Wang, Ziqing; Goodwin, J. Shawn; Lee, Eun Sook; Block, Michelle L.; Allsbrook, Matthew; Mcdonald, Michael; Fan, Guo Huang.

In: Journal of Neuroscience, Vol. 28, No. 45, 05.11.2008, p. 11622-11634.

Research output: Contribution to journalArticle

Ding, Yun ; Qiao, Aimin ; Wang, Ziqing ; Goodwin, J. Shawn ; Lee, Eun Sook ; Block, Michelle L. ; Allsbrook, Matthew ; Mcdonald, Michael ; Fan, Guo Huang. / Retinoic acid attenuates β-amyloid deposition and rescues memory deficits in an Alzheimer's disease transgenic mouse model. In: Journal of Neuroscience. 2008 ; Vol. 28, No. 45. pp. 11622-11634.
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