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Cited by 35Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative Diseases

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Clozapine Improves Memory Impairment and Reduces Aβ Level in the Tg-APPswe/PS1dE9 Mouse Model of Alzheimer’s Disease

Choi, Yura, Jeong, Ha Jin, Liu, Quan Feng, Oh, Seung Tack, Koo, Byung-Soo, Kim, Yeni, Chung, In-Won, Kim, Yong Sik, Jeon, Songhee·2017·Molecular Neurobiology
DOI 10.1007/s12035-015-9636-x
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Abstract

Alzheimer's disease (AD) is a progressive degenerative condition. In order to treat AD, the use of a "drug repositioning" or "repurposing" approach with potential disease-modifying compounds has been increased. The new generation antipsychotics are commonly used in AD and other dementias for the treatment of psychosis and behavioral symptoms, and several animal models have shown the effects of these potential disease-modifying compounds. In this study, we examined whether long-term clozapine treatment could reduce amyloid beta (Aβ) deposition and cognitive impairment in transgenic mice of AD, Tg-APPswe/PS1dE9. AD mice were fed clozapine at 20 mg/kg/day for 3 months from 4.5 months of age. Intake of clozapine improved the Aβ-induced memory impairment and suppressed Aβ levels and plaque deposition in the brain of AD mice. Clozapine upregulated Trk, brain-derived neurotrophic factor, cyclin-dependent kinase-5, and p35 in the cortex and hippocampus of AD mice and activated AMP-activated protein kinase (AMPK). As a downstream effector of AMPK, beta-secretase expression was decreased by clozapine administration. Moreover, clozapine-phosphorylated synapsin I at Ser9 and Ser549 sites in the hippocampus and cortex of AD mice, which may be involved in synaptic strength. This study suggests that as one of candidate for multi-target approach of AD treatment, clozapine is proposed as a therapeutic drug for treatment of AD patients.

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  • Clozapine was initially proposed by a study published in 2016, with subsequent support in five studies published between 2017 and 2022.

    “Clozapine was initially proposed by a study published in 2016 (Issa et al., 2016), with subsequent support in five studies published between 2017 and 2022 (Choi et al., 2017;Chen et al., 2021;Chrétien et al., 2021;Gerring et al., 2021;Soleimani Zakeri et al., 2021).”

    From Drug repurposing for Alzheimer’s disease from 2012–2022—a 10-year literature review (2023) · cites this paper as Choi et al., 2017

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Metadata

Authors
Choi, Y., Jeong, H. J., Liu, Q. F., Oh, S. T., Koo, B.-S., Kim, Y., Chung, I.-W., Kim, Y. S., & Jeon, S.
Affiliations
Dongguk University (KR)
Corresponding author
  • Kim, Yeni
  • Kim, Yong Sik
  • Jeon, Songhee
ORCID
Venue
Molecular Neurobiology
Publisher
Springer Science and Business Media LLC
Published
2016-01-07
Volume
54
Issue
1
Pages
450-460
ISSN
  • 0893-7648 (ISSN-L)
  • 1559-1182
DOI
10.1007/s12035-015-9636-x
OpenAlex
W2228991189
Cited by
35
References
0
Citations by year
2026: 3 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 1
FWCI
2.41
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Molecular Neurobiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
Keywords
clozapine, Alzheimer's disease, amyloid-beta, memory impairment, drug repurposing, antipsychotic drugs, amyloid plaques, beta-secretase, AMPK, synapsin I phosphorylation, cyclin-dependent kinase 5, brain-derived neurotrophic factor, Trk receptors, hippocampus, cortex, multi-target therapy
MeSH terms
Alzheimer Disease, Animals, Clozapine, Male, Memory Disorders, Mice, Inbred C57BL, Mice, Transgenic, Peptide Fragments, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Mice, Presenilin-1

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