阿尔茨海默病患者外周血淋巴细胞G1/S检验点功能障碍研究

Objective Throuth detecting G1 block effection induced by a special G1S transition blocker: rapamycin in lymphocytes from patients clinically diagnosed as Alzheimer's Disease (AD), we hoped to find a novel peripheral biomarker or therapeutic target for AD. Methods Peripheral lymphocytes were isolated from fifty AD patients and fifty age-matched normal controls. After incubated with phytohemagglutinin (PHA) to reactivate the cell cycle for 24 hours (T24), cells were treated with rapamycin for another 24 hours (T48). Proportions of lymphocytes at G1 and S phases of cell cycle respectively were determined by flow cytometry to evaluate the function of G1S checkpoint. Results T24: Proportions of G1 phase and S phase did not show statistically differences between AD and controls（71.14%±5.25 vs 71.11%±4.94, 18.55%±3.57 vs 18.13%±3.53, P＞0.05）. T48: Proportion of G1 phase in AD cells was lower than that in controls（47.70±7.19% vs 71.05±4.14%, P＜0.01）, but proportion of S phase in AD cells was higher than that in controls（29.12±4.36% vs 15.26±3.27%, P＜0.01）. Conclusions Activated lymphocytes from AD had a less pronounced G1S delay in response to rapamycin compared with those form controls. G1S checkpoint seemed to fail to function in lymphocytes from AD. The dysfunction of G1S checkpoint detectable in AD peripheral lymphocytes might provide us a novel peripheral biomarker or therapeutic target of AD.