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

• Published in: Journal of neurochemistry 2014-08, Vol.130 (3), p.432
• Main Authors: Kuwabara, Yuki, Ishizeki, Masato, Watamura, Naoto, Toba, Junya, Yoshii, Aya, Inoue, Takafumi, Ohshima, Toshio
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Mental depression; Neurochemistry; Rodents
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.12728

Alzheimer's disease (AD) is a neurodegenerative disorder that represents the most common type of dementia among elderly people. Amyloid beta (A[beta]) peptides in extracellular A[beta] plaques, produced from the amyloid precursor protein (APP) via sequential processing by [beta]- and [gamma]-secretases, impair hippocampal synaptic plasticity, and cause cognitive dysfunction in AD patients. Here, we report that A[beta] 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, A[beta] plaques were detected from 8 months and profound accumulation of A[beta] plaques was observed at 18 months of age. Biochemical analysis revealed relatively high levels of APP protein and A[beta] in the cerebellum of APPswe/PS1dE9 mice. At pre-A[beta] accumulation stage, LTD induction, and motor coordination are disturbed. These results indicate that soluble A[beta] oligomers disturb LTD induction and cerebellar function in AD mouse model. APPswe/PS1d9E mice, a commonly used Alzheimer's mouse model, have A[beta] plaques in the cerebellum after 8 months old. We show that soluble A[beta] impairs LTD induction in the cerebellar slice. APPswe/PS1d9E mice demonstrate defects of motor coordination and LTD induction in the cerebellum at the pre-A[beta] accumulation period. [PUBLICATION ABSTRACT]