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Browsing by Author "Barupal, Dinesh Kumar"
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Item Serum triglycerides in Alzheimer disease: Relation to neuroimaging and CSF biomarkers(Wolters Kluwer, 2020-05-01) Bernath, Megan M.; Bhattacharyya, Sudeepa; Nho, Kwangsik; Barupal, Dinesh Kumar; Fiehn, Oliver; Baillie, Rebecca; Risacher, Shannon L.; Arnold, Matthias; Jacobson, Tanner; Trojanowski, John Q.; Shaw, Leslie M.; Weiner, Michael W.; Doraiswamy, P. Murali; Kaddurah-Daouk, Rima; Saykin, Andrew J.; Consortium for the Alzheimer's Disease Neuroimaging Initiative and Alzheimer's Disease Metabolomics; Medicine, School of MedicineObjective 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.Item Sets of coregulated serum lipids are associated with Alzheimer's disease pathophysiology(Elsevier, 2019-09-05) Barupal, Dinesh Kumar; Baillie, Rebecca; Fan, Sili; Saykin, Andrew J.; Meikle, Peter J.; Arnold, Matthias; Nho, Kwangsik; Fiehn, Oliver; Kaddurah-Daouk, Rima; Radiology and Imaging Sciences, School of MedicineIntroduction: Comorbidity with metabolic diseases indicates that lipid metabolism plays a role in the etiology of Alzheimer's disease (AD). Comprehensive lipidomic analysis can provide new insights into the altered lipid metabolism in AD. Method: In this study, a total 349 serum lipids were measured in 806 participants enrolled in the Alzheimer's Disease Neuroimaging Initiative Phase 1 cohort and analyzed using lipid-set enrichment statistics, a data mining method to find coregulated lipid sets. Results: We found that sets of blood lipids were associated with current AD biomarkers and with AD clinical symptoms. AD diagnosis was associated with 7 of 28 lipid sets of which four also correlated with cognitive decline, including polyunsaturated fatty acids. Cerebrospinal fluid amyloid beta (Aβ1-42) correlated with glucosylceramides, lysophosphatidylcholines and unsaturated triacylglycerides; cerebrospinal fluid total tau and brain atrophy correlated with monounsaturated sphingomyelins and ceramides, in addition to EPA-containing lipids. Discussion: AD-associated lipid sets indicated that lipid desaturation, elongation, and acyl chain remodeling processes are disturbed in AD subjects. Monounsaturated lipid metabolism was important in early stages of AD, whereas the polyunsaturated lipid metabolism was associated with later stages of AD. Our study provides several new hypotheses for studying the role of lipid metabolism in AD.