Abstract
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 Aβ 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 Aβ and tau hyperphosphorylation in a triple transgenic mouse model of AD (3× Tg-AD). In this study, 4-month-old AD mice were treated with 6 µg/mL Se-Met in drinking water for 12 weeks and the effect of Se-Met on neuropathological deficits in olfactory bulb (OB) of 3× Tg-AD mice was investigated. The administration of Se-Met effectively decreased the production and deposition of Aβ by inhibiting β-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-3β (GSK-3β) 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.
Highlights
Alzheimer s disease (AD), which is pathologically defined by the presence of amyloid-β senile plaques (SPs), neurofibrillary tangles (NFTs), and neuronal loss within the brain, is an age-related neurodegenerative disease wherein patients suffer from sensory, motor, and cognitive loss [1,2]
Olfactory dysfunction is prevalent in patients with AD and mild cognitive impairment [8], as the neuropathological abnormalities in both central and peripheral olfactory systems have been described in AD patients
Studies have shown that olfactory deficit is a major part of cognitive impairment in AD and is highly correlated with Aβ deposition and tau hyperphosphorylation [11], especially those occurring in the olfactory bulb (OB) beyond the cortex and hippocampus [22,23]
Summary
Alzheimer s disease (AD), which is pathologically defined by the presence of amyloid-β senile plaques (SPs), neurofibrillary tangles (NFTs), and neuronal loss within the brain, is an age-related neurodegenerative disease wherein patients suffer from sensory, motor, and cognitive loss [1,2]. Previous studies have demonstrated that olfactory function decreases with aging and the decline in olfaction is part of the clinical phenotype in neurodegenerative disorders, including AD. In AD mice, olfactory deficits occurred before the clinical onset of cognitive deficits and coincided with AD pathology [5,6,7]. Olfactory dysfunction is prevalent in patients with AD and mild cognitive impairment [8], as the neuropathological abnormalities in both central and peripheral olfactory systems have been described in AD patients. Olfactory dysfunction has been proposed as a potential biomarker for AD diagnosis [9,10]
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