Journal
NEUROBIOLOGY OF AGING
Volume 30, Issue 8, Pages 1205-1216Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2007.11.001
Keywords
Quetiapine; APP/PS1 double transgenic mouse model; Alzheimer's disease; Memory; Plaque; beta-Amyloid; beta-Secretase
Categories
Funding
- Canadian Psychiatry Research Foundation
- Canadian Institutes of Health Research, NeuroScience Canada
- Schizophrenia Society of Saskatchewan
- Saskatchewan Health Research Foundation,
- AstraZeneca (Canada) Investigator Initiation
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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 5 mg/(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 (A beta) plaques decreased in the cortex and hippocampus of the transgenic mice. Quetiapine also decreased brain A beta 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. (C) 2007 Elsevier Inc. All rights reserved.
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