Serum triglycerides in Alzheimer disease
Megan M. Bernath, Sudeepa Bhattacharyya, Kwangsik Nho, Dinesh Kumar Barupal, Oliver Fiehn, Rebecca Baillie, Shannon L. Risacher, Matthias Arnold, Tanner Y. Jacobson, John Q. Trojanowski, Leslie M. Shaw, Michael W. Weiner, P. Murali Doraiswamy, Rima Kaddurah‐Daouk, Andrew J. Saykin
Abstract
<h3>Objective</h3> 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. <h3>Methods</h3> Serum levels of 84 TG species were measured with untargeted lipid profiling of 689 participants from the Alzheimer9s 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 [<sup>18</sup>F]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. <h3>Results</h3> 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 <i>APOE</i> ε4 allele, these principal components were significantly associated with CSF β-amyloid<sub>1–42</sub> values and entorhinal cortical thickness. <h3>Conclusion</h3> This study shows that PUTG component scores were significantly associated with diagnostic group and AD biomarkers, a finding that was more pronounced in <i>APOE</i> ε4 carriers. Replication in independent larger studies and longitudinal follow-up are warranted.