| Background and Objective:In recent years,a large number of studies have shown that there is a close relationship between lipid metabolism and the development of Alzheimer’s disease（AD）.The protein related to lipid transfer is also thought to be involved in the pathogenesis of AD.The Apolipopotein E（APOE）plays an important role in lipid metabolism as the main transporter of cholesterol in the brain.And the APOEε4 gene is the most important known genetic risk factor for AD,and its mutation will lead to AD.However,the relationship between other proteins related to lipid transport and AD remains to be further explored.Some studies have found that the levels of heart fatty acid-binding protein（HFABP）in cerebrospinal fluid were increased in patients with neurodegenerative diseases,such as Lewy body dementia and vascular dementia.Therefore,in this study,we explored the relationship between cerebrospinal fluid HFABP and cerebrospinal fluid and neuroimaging biomarkers of AD and cognitive function related indicators,and further explored the potential of CSF HFABP as a biomarker of AD.Methods:We selected 309 subjects from the Alzheimer’s neuroimaging（ADNI）database,which included 92 cognitively normal controls（CN）,148 Mild cognitive impairment（MCI）patients,and 69 patients with AD.The multiple linear regression models were used to analyze the association between CSF HFABP and AD-related phenotypes at baseline,which included CSF core biomarkers for AD,cognitive function,brain structure,and brain metabolic indicators.The mixed-effect model was used to analyze the correlation between cerebrospinal fluid HFABP and the longitudinal data about AD-related phenotypic.In the above analysis,all regression analyses were adjusted for the following variables:age,sex,education level,APOEε4 gene carrying status,cognitive diagnosis,hypertension,type 2 diabetes,hyperlipidemia,cardiovascular disease,depression,and body mass index.In addition,the ROC curve analysis was used to evaluate the value of cerebrospinal fluid core biomarkers and cerebrospinal fluid HFABP in the diagnosis of AD.And the Kaplan-Meier survival analysis was also used to investigate the relationship between cerebrospinal fluid HFABP and AD progression.The P values less than 0.05 were considered significant for all the statistical analysis.All statistical analyses and image production were performed by 3.43 version R software.Results:We found that the levels of cerebrospinal fluid HFABP were higher in patients with MCI and AD than normal controls（P<0.001）.According to the level of cerebrospinal fluid Aβ42,the study population was divided into Aβ-positive（Aβ+）group and Aβ-negative（Aβ-）group,and this difference was found to be more significant in the Aβ+group.In the baseline study,higher levels of cerebrospinal fluid HFABP were associated with higher levels of cerebrospinal fluid t-tau（P<0.001）,cerebrospinal fluid p-tau（P<0.001）,cerebrospinal fluid t-tau/Aβ42ratio,and cerebrospinal fluid p-tau/Aβ42ratio（P<0.001）,and this correlation remained significant across the different cognitive subgroup analyses.Cerebrospinal fluid HFABP has certain value in the diagnosis of AD（area under ROC curve:0.71）.In addition,we found that high levels of cerebrospinal fluid HFABP were associated with faster hippocampal atrophy（P<0.01）,faster cognitive decline（P<0.05）in longitudinal studies.In the analysis of Kaplan-Meier curves,we found that people with high levels of cerebrospinal fluid HFABP had a higher risk of AD（P<0.001）.Conclusion:Increased cerebrospinal fluid levels of HFABP is closely associated with the diagnosis of AD,cognitive decline,hippocampal atrophy,and increased risk of AD.These findings further suggest that CSF HFABP may be a reliable biomarker for AD. |
