title: Therapeutic effects of quetiapine on memory deficit and brain β-amyloid plaque pathology in a transgenic mouse model of Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Shenghua
authors.initials: S
authors.lastname: Zhu
authors.forename: Jue
authors.initials: J
authors.lastname: He
authors.forename: Ruiguo
authors.initials: R
authors.lastname: Zhang
authors.forename: Lynda
authors.initials: L
authors.lastname: Kong
authors.forename: Adrien
authors.initials: A
authors.lastname: Tempier
authors.forename: Jiming
authors.initials: J
authors.lastname: Kong
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D003987:Dibenzothiazepines / Q000494:pharmacology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology*; D058225:Plaque, Amyloid / Q000473:pathology*; D000069348:Quetiapine Fumarate
chemical_list: D003987:Dibenzothiazepines; D018696:Neuroprotective Agents; D000069348:Quetiapine Fumarate