血浆短链脂肪酸及胆汁酸与认知和AD脑脊液生物标志物的关系  

Association of plasma short-chain fatty acids and bile acids with cognitive performance and cerebrospinal fluid biomarkers in Alzheimer’s disease

作　　者：杨新新 谭兰[1] 张伟[1] YANG Xinxin;TAN Lan;ZHANG Wei(Department of Neurology,Qingdao Municipal Hospital,Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学附属青岛市市立医院神经内二科,山东青岛266071

出　　处：《青岛大学学报（医学版）》2024年第5期684-688,共5页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金重大研究计划项目(822-71475)。

摘　　要：目的探讨血浆中短链脂肪酸及胆汁酸与认知能力和阿尔茨海默病(AD)脑脊液生物标志物的关系。方法纳入来自阿尔茨海默病神经成像计划(ADNI)的1180例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,分析丁酸、脱氧胆酸与胆酸的比值(DCA∶CA)、甘氨石胆酸与鹅去氧胆酸的比值(GLCA∶CDCA)与认知能力和AD脑脊液生物标志物β淀粉样蛋白(Aβ)、总tau(t-tau)蛋白、磷酸化tau(p-tau)蛋白的横向和纵向关联。结果横向分析表明,丁酸水平与简易精神状态检查(MMSE)评分呈正相关(β=0.260,P<0.001),与Aβ水平呈正相关(β=0.231,P=0.024),与t-tau(β=-0.038,P=0.710)和p-tau(β=0.071,P=0.482)无相关性;DCA∶CA与MMSE评分呈负相关(β=-0.181,P<0.001),与Aβ(β=-0.070,P=0.126)、t-tau(β=0.042,P=0.325)和p-tau(β=0.051,P=0.229)无相关性;GLCA∶CDCA与MMSE评分呈负相关(β=-0.461,P=0.002),与Aβ(β=0.303,P=0.081)无相关性,与t-tau(β=0.415,P=0.016)和p-tau(β=0.440,P=0.009)呈正相关。纵向分析表明,血浆丁酸水平与MMSE评分呈正相关(β=0.223,P<0.001),与Aβ(β=-0.004,P=0.743)、t-tau(β=-0.005,P=0.064)和p-tau(β=0.001,P=0.892)无相关性;DCA∶CA与MMSE评分呈负相关(β=-0.067,P<0.001),与Aβ(β=-0.004,P=0.604)、t-tau(β=0.002,P=0.625)和p-tau(β=0.005,P=0.744)无相关性;GLCA∶CDCA与MMSE评分呈负相关(β=-0.274,P=0.001),与Aβ(β=-0.021,P=0.577)无相关性,与t-tau(β=0.004,P=0.879)和p-tau(β=-1.730×10^(-4),P=0.994)也无相关性。结论丁酸及胆汁酸可能是AD的潜在非侵入性生物标志物。Objective To investigate the association of plasma short-chain fatty acids and bile acids with cognitive perfor-mance and cerebrospinal fluid biomarkers in Alzheimer’s disease(AD).Methods A total of 1180 participants from the Alzheimer’s Disease Neuroimaging Initiative were enrolled as subjects,and the multiple linear regression model and the linear mixed-effects model were used to investigate the cross-sectionaland longitudinal correlations of butyric acid,deoxycholic acid/cholic acid ratio(DCA∶CA),and glycolithocholicacid/chenodeoxycholic acidratio(GLCA∶CDCA)with cognitive performance and AD cerebrospinal fluid biomarkers(β-amyloid(Aβ),total tau(t-tau)protein,and phosphorylated tau(p-tau)).Results The cross-sectional analysis showed that butyric acid level was positively correlated with Mini-Mental State Examination(MMSE)score(β=0.260,P<0.001)and Aβlevel(β=0.231,P=0.024),while it was not correlated with t-tau(β=-0.038,P=0.710)and p-tau(β=0.071,P=0.482).DCA∶CA was negatively correlated with MMSE score(β=-0.181,P<0.001)and was not correlated with Aβ(β=-0.070,P=0.126),t-tau(β=0.042,P=0.325),and p-tau(β=0.051,P=0.229).GLCA∶CDCA was negatively correlated with MMSE score(β=-0.461,P=0.002)and was not correlated with Aβ(β=0.303,P=0.081),while it was positively correlated with t-tau(β=0.415,P=0.016)and p-tau(β=0.440,P=0.009).The longitudinal analysis showed that plasma butyric acid level was positively correlated with MMSE score(β=0.223,P<0.001)and was not correlated with Aβ(β=-0.004,P=0.743),t-tau(β=-0.005,P=0.064),and p-tau(β=0.001,P=0.892);DCA∶CA was negatively correlated with MMSE score(β=-0.067,P<0.001)and was not correlated with Aβ(β=-0.004,P=0.604),t-tau(β=0.002,P=0.625),and p-tau(β=0.005,P=0.744);GLCA∶CDCA was negatively correlated with MMSE score(β=-0.274,P=0.001)and was not correlated with Aβ(β=-0.021,P=0.577),t-tau(β=0.004,P=0.879)and p-tau(β=-1.730×10^(-4),P=0.994).Conclusion Butyric acid and bile acids may be potential noninvasive biomarkers for AD.

关 键 词：阿尔茨海默病 丁酸盐类 胆汁酸类 生物标记 

分 类 号：R741.04[医药卫生—神经病学与精神病学]