非糖尿病非痴呆人群空腹血糖与AD脑脊液生物标志物关系

Association of fasting blood glucose with cerebrospinal fluid biomarkers for Alzheimer’s disease in the non-diabetic population without dementia

目的探讨非糖尿病非痴呆人群空腹血糖(FBG)水平与阿尔茨海默病(AD)脑脊液生物标志物的关联。方法从AD神经影像学数据库中选取1158名非糖尿病非痴呆参与者作为研究对象,分别采用多元线性回归模型和线性混合效应模型,分析FBG水平与AD脑脊液生物标志物β淀粉样蛋白(Aβ)、总tau(t-tau)蛋白和磷酸化tau(p-tau)蛋白的横向和纵向关联。结果横截面分析显示,FBG水平与t-tau(β=0.124,P=0.001)和p-tau(β=0.113,P=0.003)呈正相关,与Aβ42无相关性(β=0.067,P=0.144);FBG水平与t-tau(β<0.001,P=0.025)和p-tau(β<0.001,P=0.014)的纵向积累有关,与Aβ42的纵向变化无关(β=-0.004,P=0.716)。亚组分析显示,在女性参与者中,FBG水平与t-tau(β=0.119,P=0.002)和p-tau(β=0.129,P=0.024)呈正向相关,而在男性中FBG仅与t-tau呈正相关(β=0.101,P=0.047);FBG与t-tau(β=0.118,P=0.004)和p-tau(β=0.110,P=0.007)的正向关联仅在65岁以上的参与者中存在;在APOEε4基因携带者中FBG水平升高与t-tau(β=0.160,P=0.012)和p-tau(β=0.154,P=0.017)的增长相关。结论FBG水平与脑脊液中t-tau、p-tau存在显著正相关性,FBG水平降低可能对AD病理改变有保护作用。

Objective To investigate the association of fasting blood glucose(FBG)with cerebrospinal fluid biomarkers for Alzheimer’s disease(AD)in the non-diabetic population without dementia.Methods A total of 1158 non-diabetic participants without dementia were selected as research subjects from AD Neuroimaging Initiative database.The multiple linear regression mo-del and the linear mixed-effects model were used to investigate the cross-sectional and longitudinal relationships between FBG level and the cerebrospinal fluid biomarkers for AD includingβ-amyloid(Aβ),total tau(t-tau),and phosphorylated tau(p-tau).Results The cross-sectional analysis showed that FBG was positively associated with t-tau(β=0.124,P=0.001)and p-tau(β=0.113,P=0.003)and was not associated with Aβ42(β=0.067,P=0.144);FBG level was associated with the longitudinal accumulation of t-tau(β<0.001,P=0.025)and p-tau(β<0.001,P=0.014)and was not associated with the longitudinal changes of Aβ42(β=-0.004,P=0.716).The subgroup analysis showed that in female participants,FBG level was positively associated with t-tau(β=0.119,P=0.002)and p-tau(β=0.129,P=0.024),while in male participants,FBG was only positively associated with t-tau(β=0.101,P=0.047).FBG was positively associated with t-tau(β=0.118,P=0.004)and p-tau(β=0.110,P=0.007)only in participants aged 65 years and above.In APOEε4 gene carriers,the increase in FBG level was associated with the increases in t-tau(β=0.160,P=0.012)and p-tau(β=0.154,P=0.017).Conclusion FBG level is positively associated with t-tau and p-tau in cerebrospinal fluid,and lowering FBG level may have a protective effect against pathological changes in AD.