丙酮酸激酶M型同工酶在阿尔茨海默病中的表达特点

Analysis of the expression characteristics of pyruvate kinase M-type isoenzyme in Alzheimer’s disease

目的探讨脑脊液(CSF)中丙酮酸激酶M型同工酶(PKM)的表达特点及其与阿尔茨海默病(AD)核心标志物的相关性。方法纳入ADNI数据库中痴呆(AD)组62例,轻度认知障碍(MCI)组130例,以及健康对照(CN)组83例,共275例研究对象。分析各组间CSF PKM水平差异以及PKM与AD生物标志物水平之间的相关性。结果与CN组相比,MCI组及AD组CSF PKM水平均显著升高(P<0.05),与非载脂蛋白Eε4(APOEε4)基因携带者相比,该基因携带者PKM水平显著升高(P=0.011)。MCI组及AD组患者CSF PKM水平与CSF中总tau蛋白(t-tau)及磷酸化tau蛋白(p-tau)水平呈相关性(MCI:r=0.802,P<0.001;r=0.759,P<0.001。AD:r=0.783,P<0.001;r=0.715,P<0.001)。结论AD及MCI患者中CSF PKM水平与CN组相比显著升高,其与tau蛋白呈正相关,且与APOEε4基因携带情况相关,提示其有待成为阿尔茨海默病的诊断标志物和干预靶点。

Objective To investigate the expression characteristics of pyruvate kinase M-type isoenzyme(PKM)in cerebrospinal fluid(CSF)and its correlation with the core markers of Alzheimer’s disease(AD).Methods The included 62cases of dementia(AD),130cases of mild cognitive impairment(MCI)and 83cases of healthy control(CN),a total of 275subjects are from ADNI database.The differences in CSF PKM levels among the groups and the correlation between PKM and AD biomarker levels were analyzed.Results Compared with CN group,CSF PKM levels in MCI group and AD group were significantly increased(P<0.05)and PKM level in apolipoprotein Eε4(APOEε4)gene carriers was significantly increased compared with non-APOEε4gene carrier(P=0.011).The levels of CSF PKM in MCI and AD groups were correlated with the levels of total tau protein(t-tau)and phosphorylated tau protein(p-tau)in CSF(MCI:r=0.802,P<0.001;r=0.783,P<0.001.AD:r=0.759,P<0.001;r=0.715,P<0.001).Conclusion The levels of CSF PKM in AD and MCI patients were significantly higher than that in CN group,and it was positively correlated with tau protein and APOEε4gene carrying,suggesting that it should be used as a diagnostic marker and intervention target for Alzheimer’s disease.