title: Impairments of long-term depression induction and motor coordination precede Aβ accumulation in the cerebellum of APPswe/PS1dE9 double transgenic mice.
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 onths 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.
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kuwabara
authors.forename: Masato
authors.initials: M
authors.lastname: Ishizeki
authors.forename: Naoto
authors.initials: N
authors.lastname: Watamura
authors.forename: Junya
authors.initials: J
authors.lastname: Toba
authors.forename: Aya
authors.initials: A
authors.lastname: Yoshii
authors.forename: Takafumi
authors.initials: T
authors.lastname: Inoue
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohshima
mesh_terms: D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002531:Cerebellum / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism*; D011597:Psychomotor Performance / Q000502:physiology*; D012018:Reflex / Q000235:genetics / Q000502:physiology; D013569:Synapses / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; amyloid beta; amyloid precursor protein; cerebellum; long-term depression; treatment