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Objective To investigate the association of triglyceride (TG) principal component scores with Alzheimer’s disease (AD) and the “A/T/N/V” (Amyloid, Tau, Neurodegeneration, and Cerebrovascular disease) biomarkers for AD. Methods Serum levels of 84 TG species were measured using untargeted lipid profiling of 689 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort including 190 cognitively normal older adults (CN) and 339 mild cognitive impairment (MCI) and 160 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]FDG-PET) were assessed using a multivariate generalized linear model (GLM) approach. In both cases, the Bonferroni method of adjustment was employed to correct for multiple comparisons. Results The 84 TGs yielded 9 principal components, two 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 APOE ε4 allele, these principal components were significantly associated with CSF amyloid-β1-42 values and entorhinal cortical thickness. Conclusions This study shows PUTG component scores 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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