Selenomethionine Ameliorates Neuropathology in the Olfactory Bulb of a Triple Transgenic Mouse Model of Alzheimer's Disease

Olfactory dysfunction is an early and common symptom in Alzheimer's disease (AD) and is reported to be related to several pathologic changes, including the deposition of A beta and hyperphosphorylated tau protein as well as synaptic impairment. Selenomethionine (Se-Met), the major form of selenium in animals and humans, may be a promising therapeutic option for AD as it decreases the deposition of A beta and tau hyperphosphorylation in a triple transgenic mouse model of AD (3x Tg-AD). In this study, 4-month-old AD mice were treated with 6 mu g/mL Se-Met in drinking water for 12 weeks and the effect of Se-Met on neuropathological deficits in olfactory bulb (OB) of 3x Tg-AD mice was investigated. The administration of Se-Met effectively decreased the production and deposition of A beta by inhibiting beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)-regulated amyloid precursor protein (APP) processing and reduced the level of total tau and phosphorylated tau, which depended on depressing the activity and expression of glycogen synthase kinase-3 beta (GSK-3 beta) and cyclin-dependent kinase 5 (CDK5). Meanwhile, Se-Met reduced glial activation, relieved neuroinflammation and attenuated neuronal cell death in the OB of AD mice. So Se-Met could improve pathologic changes of AD in the OB, which further demonstrated the potential therapeutic effect of Se-Met in AD.