Study On The Changes Of Fatty Acid Composition And Metabolism In Peripheral Blood Of Alzheimer’s Disease

BackgroundThe pathogenesis of Alzheimer’s disease(AD)has not been elucidated,therefore there are no effective measures for early diagnosis,prevention and treatment.Studies have shown that there is abnormal fatty acid composition in the brain of AD patients,but further studies are needed to clarify the characteristic changes of AD fatty acids.It is necessary to study whether the abnormal fatty acid composition of AD is related to the metabolic pathway of fatty acids in the body.ObjectiveThe aim of this study is to compare the composition of fatty acids and the expression of fatty acid metabolism related factors in peripheral blood between normal old people and patients with AD to find experimental evidences for the relationship between fatty acid metabolism and Alzheimer’s disease,further to reveal the pathogenesis and a new diagnostic marker of Alzheimer disease.Methods1.Selection of research objects and sample collection: subjects(30 cases of AD group and normal group)were selected according to NINCDS-ADRDA diagnostic criteria and exclusion criteria.Fasting venous blood was obtained from all cases,and serum and peripheral blood mononuclear cells were isolated.2.Determination of blood lipids,blood glucose and serum fatty acid composition: the contents of serum glucose(GLU),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and free fatty acid(FFA)were determined by kit,and fatty acid composition were analyzed by gas chromatography.3.Determination of the expression of fatty acid metabolism related factors: peripheral blood mononuclear cells were used to measure the expression of carnitine palmitoyltransferase 1(CPT1)of mitochondrial beta-oxidation key enzyme,acyl-coenzyme A oxidase 1(ACOX1)of peroxisomal beta-oxidation key enzymes and peroxisome proliferator-activated receptor alpha(PPARα)by real-time fluorescent quantitative PCR and Western blotting.Results1.The changes of serum blood lipid,blood glucose and fatty acid composition:compared with normal group,HDL-C content was significantly decreased in AD group(P<0.05),but the changes of GLU,TC,TG,LDL-C and FFA in AD group have no statistical significance(P>0.05);There was no significant change in the content of total saturated fatty acid(SFA)in AD group(P>0.05),but C16:0 was significantly decreased(P<0.05),and the contents of C24:0 and total long chain saturated fatty acids(ΣVLCSFA)were increased significantly(P<0.01).The content of total monounsaturated fatty acids(ΣMUAF)had a rising trend in AD group(P=0.12),and C16:1 was increased obviously(P<0.05).The contents of total polyunsaturated fatty acids(ΣPUFA),C18:2 and C20:4were significantly decreased(P<0.05),while the contents of C20:2 and C20:3n6 were increased(P<0.05).2.The changes of CPT1,ACOX1 and PPARα: compared with normal group,PPARαprotein expression was increased in AD group(P<0.05),but there were no significant changes with CPT1 and ACOX1 protein levels(P>0.05).There were no significant changes of CPT1,ACOX1 and PPARα mRNA levels between AD group and normal group(P>0.05).3.Linear correlation analysis: MMSE scores were positively correlated with serum C16:0,C18:2n6,C20:4n6,C20:5n3,ΣPUFA,ΣPUFAn6(P<0.05)and negatively correlated with C20:3n6(P<0.05).There was no linear correlation between MMSE scores and ΣVLCSFA,ΣSFA,ΣMUAF(P>0.05).MMSE scores were negatively correlated withPPARα protein expression(P<0.05),but MMSE scores were not correlated with the protein expression of ACOX1 and CPT1(P>0.05).Serum ΣPUFAn3 contents were positively correlated with the protein expression of CPT1(P<0.05),and ΣVLCSFA contents were positively correlated with the protein expression of ACOX1(P<0.05),but fatty acid contents were not correlated with the protein expression of PPARα(P>0.05).ConclusionThere are some abnormities of fatty acid composition and metabolism in AD,including the increased very long chain saturated fatty acids,the decreased polyunsaturated fatty acids and the increased of PPARα expression.Abnormal fatty acid metabolism may be one of the causes of AD,and the fatty acid spectrum is expected to be a potential diagnostic biomarker for AD.