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 1 180 participants from the Alzhei-mer'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 cere-brospinal fluid biomarkers(β-amyloid(Aβ),total tau(t-tau)protein,and phosphorylated tau(p-tau)).Results The cross-sec-tional analysis showed that butyric acid level was positively correlated with Mini-Mental State Examination(MMSE)score(β=0.260,P＜0.001)and Aβ level(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 positive-ly 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 bu-tyric 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.
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