Impairments of long-term depression induction and motor coordination precede Aβ accumulation in the cerebellum of APPswe/PS1dE9 double transgenic mice

Yuki Kuwabara, Masato Ishizeki, Naoto Watamura, Junya Toba, Aya Yoshii, Takafumi Inoue, Toshio Ohshima

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    Alzheimer's disease (AD) is a neurodegenerative disorder that represents the most common type of dementia among elderly people. Amyloid beta (Aβ) peptides in extracellular Aβ plaques, produced from the amyloid precursor protein (APP) via sequential processing by β- and γ-secretases, impair hippocampal synaptic plasticity, and cause cognitive dysfunction in AD patients. Here, we report that Aβ peptides also impair another form of synaptic plasticity; cerebellar long-term depression (LTD). In the cerebellum of commonly used AD mouse model, APPswe/PS1dE9 mice, Aβ plaques were detected from 8 months and profound accumulation of Aβ plaques was observed at 18 months of age. Biochemical analysis revealed relatively high levels of APP protein and Aβ in the cerebellum of APPswe/PS1dE9 mice. At pre-Aβ accumulation stage, LTD induction, and motor coordination are disturbed. These results indicate that soluble Aβ oligomers disturb LTD induction and cerebellar function in AD mouse model.

    Original languageEnglish
    Pages (from-to)432-443
    Number of pages12
    JournalJournal of Neurochemistry
    Volume130
    Issue number3
    DOIs
    Publication statusPublished - 2014

    Fingerprint

    Cerebellum
    Transgenic Mice
    Alzheimer Disease
    Depression
    Neuronal Plasticity
    Amyloid beta-Protein Precursor
    Plasticity
    Amyloid Precursor Protein Secretases
    Peptides
    Amyloid beta-Peptides
    Staphylococcal Protein A
    Oligomers
    Amyloid
    Neurodegenerative Diseases
    Dementia
    Processing

    Keywords

    • Alzheimer's disease
    • amyloid beta
    • amyloid precursor protein
    • cerebellum
    • long-term depression
    • treatment

    ASJC Scopus subject areas

    • Biochemistry
    • Cellular and Molecular Neuroscience

    Cite this

    Impairments of long-term depression induction and motor coordination precede Aβ accumulation in the cerebellum of APPswe/PS1dE9 double transgenic mice. / Kuwabara, Yuki; Ishizeki, Masato; Watamura, Naoto; Toba, Junya; Yoshii, Aya; Inoue, Takafumi; Ohshima, Toshio.

    In: Journal of Neurochemistry, Vol. 130, No. 3, 2014, p. 432-443.

    Research output: Contribution to journalArticle

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    AU - Ishizeki, Masato

    AU - Watamura, Naoto

    AU - Toba, Junya

    AU - Yoshii, Aya

    AU - Inoue, Takafumi

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