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A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
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Serum triglycerides in Alzheimer disease: Relation to neuroimaging and CSF biomarkers
Megan M Bernath1, Sudeepa Bhattacharyya1, Kwangsik Nho1
1From the Department of Radiology and Imaging Sciences (M.M.B., K.N., S.L.R., T.J., A.J.S.), Center for Neuroimaging, Indiana Alzheimer Disease Center (M.M.B., K.N., S.L.R., T.J., A.J.S.), Medical and Molecular Genetics Department (M.M.B., T.J., A.J.S.), and Medical Scientist Training Program (M.M.B.), Indiana University School of Medicine, Indianapolis; Department of Pediatrics (S.B.), University of Arkansas for Medical Sciences, Little Rock; Department of Environmental Medicine and Public Health (D.K.B.), Icahn School of Medicine at Mt Sinai, New York; NIH-West Coast Metabolomics Center (D.K.B., O.F.), University of California, Davis; Rosa & Co LLC (R.B.), San Carlos, CA; Institute of Bioinformatics and Systems Biology (M.A.), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Department of Pathology & Laboratory Medicine (J.Q.T., L.M.S.), University of Pennsylvania, Philadelphia; Department of Radiology (M.W.W.), Center for Imaging of Neurodegenerative Diseases, San Francisco VA Medical Center/University of California San Francisco; and Department of Psychiatry and Behavioral Sciences (M.A., P.M.D., R.K.-D.), Duke Institute of Brain Sciences (R.K.-D.), and Department of Medicine (R.K.-D.), Duke University, Durham, NC.
Objective:
To investigate the association of triglyceride (TG) principal component scores with Alzheimer disease (AD) and the amyloid, tau, neurodegeneration, and cerebrovascular disease (A/T/N/V) biomarkers for AD.
Methods:
Serum levels of 84 TG species were measured with untargeted lipid profiling of 689 participants from the Alzheimer's Disease Neuroimaging Initiative cohort, including 190 cognitively normal older adults (CN), 339 with mild cognitive impairment (MCI), and 160 with AD. Principal component analysis with factor rotation was used for dimension reduction of TG species. Differences in principal components between diagnostic groups and associations between principal components and AD biomarkers (including CSF, MRI and [18F]fluorodeoxyglucose-PET) were assessed with a generalized linear model approach. In both cases, the Bonferroni method of adjustment was used to correct for multiple comparisons.
Results:
The 84 TGs yielded 9 principal components, 2 of which, consisting of long-chain, polyunsaturated fatty acid-containing TGs (PUTGs), were significantly associated with MCI and AD. Lower levels of PUTGs were observed in MCI and AD compared to CN. PUTG principal component scores were also significantly associated with hippocampal volume and entorhinal cortical thickness. In participants carrying the APOE ε4 allele, these principal components were significantly associated with CSF β-amyloid1-42 values and entorhinal cortical thickness.
Conclusion:
This study shows that PUTG component scores were significantly associated with diagnostic group and AD biomarkers, a finding that was more pronounced in APOE ε4 carriers. Replication in independent larger studies and longitudinal follow-up are warranted.
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