4.7 Article

Serum triglycerides in Alzheimer disease: Relation to neuroimaging and CSF biomarkers

Journal

NEUROLOGY
Volume 94, Issue 20, Pages E2088-E2098

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000009436

Keywords

-

Funding

  1. National Institute on Aging [RF1 AG0151550, R01AG046171, U24 AG21886, U01AG024904-09S4, P50NS053488, R01AG19771, P30AG10133, P30AG10124, R03AG054936, K01AG049050]
  2. ADNI (NIH grant) [U01 AG024904]
  3. Department of Defense ADNI (Department of Defense award) [W81XWH-12-2-0012]
  4. National Institute of Biomedical Imaging and Bioengineering
  5. AbbVie
  6. Alzheimer's Association
  7. Alzheimer's Drug Discovery Foundation
  8. Araclon Biotech
  9. BioClinica, Inc
  10. Biogen
  11. Bristol-Myers Squibb Co
  12. CereSpir, Inc
  13. Cogstate
  14. Eisai Inc
  15. Elan Pharmaceuticals, Inc
  16. Eli Lilly and Co
  17. EuroImmun
  18. F. Hoffmann-La Roche Ltd
  19. Genentech, Inc
  20. Fujirebio
  21. GE Healthcare
  22. IXICO Ltd
  23. Janssen Alzheimer Immunotherapy Research & Development, LLC
  24. Johnson & Johnson Pharmaceutical Research & Development LLC
  25. Lumosity
  26. Lundbeck
  27. Merck Co, Inc
  28. Meso Scale Diagnostics, LLC
  29. NeuroRx Research
  30. Neurotrack Technologies
  31. Novartis Pharmaceuticals Corp
  32. Pfizer Inc
  33. Piramal Imaging
  34. Servier
  35. Takeda Pharmaceutical Co
  36. Transition Therapeutics
  37. Canadian Institutes of Health Research
  38. National Library of Medicine [R01LM011360, R01 LM012535]
  39. National Institute of Biomedical Imaging and Bioengineering [R01EB022574]
  40. Indiana Clinical and Translational Science Institute
  41. Indiana University-IU Health Strategic Neuroscience Research Initiative
  42. Indiana Clinical and Translational Sciences Institute from NIH [UL1TR002529]
  43. National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award
  44. National Institute on Aging of the NIH [F30AG063449]

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ObjectiveTo 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.MethodsSerum 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 [F-18]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.ResultsThe 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 epsilon 4 allele, these principal components were significantly associated with CSF beta -amyloid(1-42) values and entorhinal cortical thickness.ConclusionThis study shows that PUTG component scores were significantly associated with diagnostic group and AD biomarkers, a finding that was more pronounced in APOE epsilon 4 carriers. Replication in independent larger studies and longitudinal follow-up are warranted.

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