It is known that the typical feature of Alzheimer’s disease is a gradual progression of memory impairment and higher brain functions until the complete disorder of intelligence and mental activity. Significant degeneration of hippocampal neurons, the senile plaques (the main component of which is β-amyloid) and the intracellular neurofibrillary tangles in the brains of patients are the main indicators of the pathology. There is evidence that β-amyloid can directly affect the mitochondria, causing the mitochondrial permeability transition pore opening. Consequently, the damaged dendritic tree, apoptosis and necrosis of neurons appear. However, the role of mitochondrial permeability transition pore in the development of Alzheimer’s disease is not still clear. Therefore, the aim of our study was to establish the influence of cyclosporine A, mitochondrial pore blocker on calcium homeostasis and viability of hippocampal neurons at the modeling of Alzheimer’s disease. The studies were performed on hippocampal neuronal culture from Wistar neonatal rats. The animals were anesthetized by inhalation with diethyl ether and decapitated. Intracellular calcium concentration was determined by fluorescent microscopy by using the calcium-sensitive dye fura-2/AM (5 μM, 30 min), whereby the ratio of fluorescence signals at two wavelengths R = F1/F2 was measured (1). We compared the amplitude of calcium transients caused by membrane depolarization with KCl (50 mM, 5 sec) in neurons after incubation with β1-42-amyloid (Aβ; the modeling of Alzheimer’s disease) (2 μM, 24 h) and after following incubation with cyclosporine A (1.25 μM, 30 min) and Aβ (2 μM, 24 h). The viability of neurons was evaluated by confocal microscopy by using Hoechst 33258 (1 μg/ml, 20 min), the indicator of alive cells and Propidium Iodide (2 μg/ml, 10 min), the indicator of necrotic cells. We compared the fluorescence ratio of each of these stains relatively to all fluorescent neurons after incubation with Aβ (2 μM, 24 h) and after following incubation with cyclosporine A (1.25 μM, 30 min) and Aβ (2 μM, 24 h).We have found that after incubation with Aβ the amplitude of calcium transients in neurons was equal to 3.565 ± 0.133 (n = 80). This value was decreased to 54 ± 4 % (P ≤ 0.001) and accounted for 1.912 ± 0.149 (n = 23) after cyclosporine A treatment. We have found 59 ± 4 % (P ≤ 0.001, n = 1601) of necrotic neurons relatively to all cells after incubation with Aβ. This value was decreased to 42 ± 6 % (P ≤ 0.001, n = 1134) after cyclosporine A treatment. Thus, we supposed that the mitochondrial permeability transition pore is directly involved in the redistribution of calcium in hippocampal neurons, and consequently can participate in necrotic death of these cells during the development of Alzheimer’s disease.