Impairments of long-term depression induction and motor coordination precede Aß 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 (Aß) peptides in extracellular Aß plaques, produced from the amyloid precursor protein (APP) via sequential processing by ß- and γ-secretases, impair hippocampal synaptic plasticity, and cause cognitive dysfunction in AD patients. Here, we report that Aß 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, Aß plaques were detected from 8 months and profound accumulation of Aß plaques was observed at 18 onths of age. Biochemical analysis revealed relatively high levels of APP protein and Aß in the cerebellum of APPswe/PS1dE9 mice. At pre-Aß accumulation stage, LTD induction, and motor coordination are disturbed. These results indicate that soluble Aß oligomers disturb LTD induction and cerebellar function in AD mouse model.