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  • Title: Beneficial effects of quetiapine in a transgenic mouse model of Alzheimer's disease.
    Author: He J, Luo H, Yan B, Yu Y, Wang H, Wei Z, Zhang Y, Xu H, Tempier A, Li X, Li XM.
    Journal: Neurobiol Aging; 2009 Aug; 30(8):1205-16. PubMed ID: 18079026.
    Abstract:
    Previous studies have suggested that quetiapine, an atypical antipsychotic drug, may have beneficial effects on cognitive impairment, and be a neuroprotectant in treating neurodegenerative diseases. In the present study, we investigated the effects of quetiapine on memory impairment and pathological changes in an amyloid precursor protein (APP)/presenilin-1 (PS-1) double transgenic mouse model of Alzheimer's disease (AD). Non-transgenic and transgenic mice were treated with quetiapine (0, 2.5, or 5mg/(kg day)) for 1, 4, and 7 months in drinking water from the age of 2 months. After 4 and 7 months of continuous quetiapine administration, memory impairment was prevented, and the number of beta-amyloid (Abeta) plaques decreased in the cortex and hippocampus of the transgenic mice. Quetiapine also decreased brain Abeta peptides, beta-secretase activity and expression, and the level of C99 (an APP C-terminal fragment following cleavage by beta-secretase) in the transgenic mice. Furthermore, quetiapine attenuated anxiety-like behavior, up-regulated cerebral Bcl-2 protein, and decreased cerebral nitrotyrosine in the transgenic mice. These findings suggest that quetiapine can alleviate cognitive impairment and pathological changes in an APP/PS1 double transgenic mouse model of AD, and further indicate that quetiapine may have preventive effects in the treatment of AD.
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