Our previous study has shown the preventive effects of quetiapine, an atypical antipsychotic drug, on memory
impairment and brain pathological changes in a mouse model of Alzheimer’s disease (AD). The aim of the present study
was to evaluate the therapeutic effects of quetiapine on memory deficit and neuropathology in an amyloid precursor protein
(APP)/presenilin-1 (PS1) double transgenic mouse model of AD. The APP/PS1 mice started to have detectable brain
β-amyloid (Aβ) at 3 months of age. Non-transgenic and transgenic mice were treated with quetiapine (0, 2.5, or 5 mg/(kg
day)) in drinking water from the age of 4 months. After 8 months of continuous quetiapine administration, memory deficit
was reversed and brain Aβ plaque pathology was attenuated in the AD mice. Quetiapine also decreased the soluble Aβ
peptide levels in brain and cerebrospinal fluid (CSF), and attenuated the decreased synaptic protein levels in the AD mice.
Furthermore, quetiapine normalized the abnormal activity of glycogen synthase kinase-3β (GSK-3β), an AD-involved
kinase, in the AD mice. These results suggest that quetiapine can treat and alleviate the neuropathology in an APP/PS1
transgenic mouse model of AD, and indicate that quetiapine may have therapeutic effects in the treatment of AD.
Keywords: Alzheimer’s disease, APP/PS1 double transgenic mouse model, Quetiapine, β-amyloid, Plaque, Memory
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