Neuroprotective Effects of Salidroside in a Mouse Model of Alzheimer’s Disease

Alzheimer's disease (AD), the most common form of dementia worldwide, is characterized by pathological hallmarks like β-amyloid peptide (Aβ) and clinical manifestations including cognitive impairment, psychiatry disorders, and behavioral changes. Salidroside (Sal) extracted from Rhodiola rosea L. showed protective effects against Aβ-induced neurotoxicity in a Drosophila AD model in our previous research. In the present study, daily doses of Sal were administered to APP/PS1 mice, a mouse model of AD, and several parameters were tested, including behavioral performance, Aβ status, levels of synapse-related proteins, and levels of PI3K/Akt targets of mTOR cell signaling pathway proteins. The behavioral testing showed an improvement in locomotor activity in the APP/PS1 mice after the administration of Sal. Treatment with Sal decreased both the soluble and insoluble Aβ levels and increased the expression of PSD95, NMDAR1, and calmodulin-dependent protein kinase II. The phosphatidylinositide PI3K/Akt/mTOR signaling was upregulated, which was in accordance with the above improvements from Sal treatment. Our findings suggested that Sal may protect the damaged synapses of the neurons in the APP/PS1 mice.