알쯔하이머형 치매 환자의 단핵세포 증식과 싸이토카인 생성에 대한 β-아밀로이드 펩티드의 작용

Effects of β-amyloid Peptide on the Proliferation and Cytokine Production of Mononuclear Cells from Patients with Dementia of the Alzheimer’s Type

연구목적： 알쯔하이머 치매의 병인론에 면역성 기전이 개입된다는 가설을 확인하고자 본 연구를 행하였다. 방 법： 알쯔하이머 치매 19명, 혈관성 치매 22명, 정상 노인 19명에서 말초 혈액 단핵세포를 분리하여 phytohemagglutinin- P(PHA-P) 및 1-40의 β-아밀로이드(Aβ)로 자극하여 세포 증식 정도를 비교하였으며, 배양 상청액에서 interleukin-1β(IL-1β)와 tumor necrosis factor-α(TNF-α)를 효소결합면역흡착분석법 으로 측정하였다. 결 과： 1) PHA-P 자극에 의한 단핵 세포의 증식은 세 군에서 차이가 없었다. 2) Aβ 자극은 단핵세포의 증식에 현저한 영향이 없었으나, 알쯔하이머 치매군이 혈관성 치매군과 대조군 에 비하여 유의하게 많이 증식되었다. 3) 배양한 단핵세포 상청액의 IL-1β는 혈관성 치매군이 가장 높았으며, Aβ 자극 후에도 혈관성 치매군 에서 가장 높았으나 자극 전후를 비교할 때, 알쯔하이머 치매군에서 가장 현저하게 자극 후 IL-1β 생성이 증 가되었다. 4) 배양한 단핵세포 상청액의 TNF-α는 알쯔하이머 치매군이 대조군보다 유의하게 높았으며, Aβ 자극 후에도 알쯔하이머 치매군이 대조군보다 유의하게 높았다. 결 론： 이상의 실험을 통하여 알쯔하이머 치매군의 말초 혈액 단핵세포가 Aβ 자극에 따라 나타내는 과도한 면역 반응을 관찰하였다. 이는 알쯔하이머 치매의 병태생리에서 Aβ 침착에 따른 면역성 반응이 중요한 역할을 한다 는 것을 시사한다.

Objectives：Deposition of the β-amyloid(Aβ) peptide in the senile plaque has been thought as a major etiologic factor for the development of Alzheimer’s disease. Among the hypotheses suggested to explain the mechanism by which Aβ causes Alzheimer’s disease, the immune processes have been considered as crucial events in the pathophysiology of the Alzheimer’s disease. This study examined the effects of Aβ on the proliferation and the production of IL-1β(interleukin-1β) and TNF-α(tumor necrosis factor-α) in peripheral blood mononuclear cells isolated from the patients with Alzheimer s disease, vascular dementia, and normal elderly control subjects. Methods：Nineteen patients with Alzheimer’s disease, 22 patients with vascular dementia, and 19 controls were participated in this study. Peripheral blood mononuclear cells were obtained from each donors, and subjected to the proliferation assays in response to the stimulation of phytohemagglutinin- P(PHA-P) and Aβ. The levels of IL-1β and TNF-α from the culture supernatants of the cells before and after the stimulation of Aβ were also determined by enzyme linked immunosorbent assay. Results：The results were as follows； 1) The proliferation of mononuclear cells in response to PHA-P were not different among three groups. 2) When compared to PHA-P, the proliferation responses of mononuclear cells to Aβ were insignificant in all experimental groups. However Alzheimer’s disease group showed greater stimulation index than vascular dementia and controls. 3) IL-1β production was higher in the vascular dementia group than Alzheimer’s disease and control groups both before and after the stimulation of Aβ. However the stimulation ratio of before and after Aβ stimulation was highest in Alzheimer s disease group. 4) TNF-α production was higher in Alzheimer’s disease group than controls both before and after the stimulation of Aβ. Conclusion：These findings suggest that the immune responses to the stimulation of Aβ may be enhanced in patients with Alzheimer’s disease compared to vascular dementia and control groups, supporting the immune hypothesis for the pathophysiology of Alzheimer s disease.