The role of STIM2 - nSOCE signaling pathway was investigated in model of Alzheimer’s disease (AD), 5×FAD mice, that express amyloid and presenilin toxicity simultaneously. It was observed that expression of STIM2 protein was downregulated in the hippocampus of adult 5×FAD mice at the ages of 4 and 6 months. It was shown that expression of PSD95 protein was downregulated together with STIM2 protein. It was established that hyperexpression of STIM2 protein in the hippocampus of adult mouse was able to lower the amount of amyloid plaques in the cortex of 5×FAD mice by three times. The observed data confirms scientific hypothesis that activation of STIM2-dependent store-operated calcium entry can have therapeutic effect for treatment in AD.