Alzheimer’s disease (AD) is the most common neurodegenerative disorder of the central nervous system. Current
approaches for AD treatment only ameliorate symptoms. Therapeutic strategies that target the pathological processes
of the disease remain elusive. Fluoxetine (FLX) is one of the most widely used antidepressants for the treatment of depression
and anxiety associated with AD, however, it is unknown if the drug affects the pathogenesis of the disease. We
showed that FLX improved spatial memory, learning and emotional behaviors of APP/PS1 mice, a well characterized
model of AD. In the same mice, FLX effectively prevented the protein loss of synaptophysin (SYP) and microtubuleassociated
protein 2 (MAP2). FLX was unable to prevent plaque formation, but significantly lowered high levels of soluble
β-amyloid (Aβ) in brain tissue, cerebrospinal fluid (CSF) and blood sera. FLX also effectively inhibited the phosphorylation
of amyloid precursor protein (APP) at T668, which may be a possible mechanism of the reduced Aβ production
in APP/PS1 mouse after treatment.
Keywords: Amyloid precursor protein (APP), Alzheimer’s disease (AD), behavior, fluoxetine, soluble Aβ.
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