Serum triglycerides in Alzheimer disease: Relation to neuroimaging and CSF biomarkers - PubMed (original) (raw)

. 2020 May 19;94(20):e2088-e2098.

doi: 10.1212/WNL.0000000000009436. Epub 2020 May 1.

Sudeepa Bhattacharyya 1, Kwangsik Nho 1, Dinesh Kumar Barupal 1, Oliver Fiehn 1, Rebecca Baillie 1, Shannon L Risacher 1, Matthias Arnold 1, Tanner Jacobson 1, John Q Trojanowski 1, Leslie M Shaw 1, Michael W Weiner 1, P Murali Doraiswamy 1, Rima Kaddurah-Daouk 1, Andrew J Saykin 2; Alzheimer's Disease Neuroimaging Initiative and Alzheimer's Disease Metabolomics Consortium

Affiliations

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

Megan M Bernath et al. Neurology. 2020.

Abstract

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.

© 2020 American Academy of Neurology.

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Figures

Figure 1

Figure 1. Group differences of PCs of TGs with diagnosis groups (CN, MCI, and AD)

A series of 6 separate generalized linear models were performed to assess diagnostic group (cognitively normal [CN], mild cognitive impairment [MCI], Alzheimer disease [AD]) differences across all principal components (PCs). Bonferroni adjustment was used to correct for significance of diagnostic group differences across the 9 PCs of triglycerides (TGs). Covariates included age, sex, body mass index, total TGs, and APOE ε4 status. Values are mean ± standard error. #p = 0.0533, *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 2

Figure 2. Association of TG PC3 and PC5 with A/T/N/V biomarkers for Alzheimer disease

A series of 14 separate post hoc linear regressions were performed to assess the association of 7 amyloid, tau, neurodegeneration, and cerebrovascular disease (A/T/N/V) biomarkers with principal component (PC) 3 and PC5. Bonferroni adjustment was used to correct for the 14 association analyses between PC3, PC5, and 7 A/T/N/V endophenotypes. Covariates included age, sex, body mass index, total triglycerides (TGs), and APOE ε4 status for all A/T/N/V phenotypes. For MRI biomarkers, we also included years of education and intracranial volume as additional covariates. The y-axis colors represent standardized β values from the linear regression analysis, with shades of red indicating a positive standardized β value and gray scale indicating a negative standardized β value. Aβ = β-amyloid1-42 peptide; FDG global cortex = cortical glucose standardized uptake value ratio measured from [18F]fluorodeoxyglucose-PET scans; p-tau = tau phosphorylated at threonine 181; t-tau = total tau; WMHI = white matter hyperintensity total volume. *p < 0.05, **p < 0.01.

Figure 3

Figure 3. Whole-brain surface-based analysis of cortical thickness for PC3 and PC5

(A) Whole-brain analysis of cortical thickness across the brain surface was performed to identify the association of 2 principal components (PCs) ([A] PC3 and [B] PC5) with brain structure shown as a t value map and a p value map. Statistical maps were thresholded using a random field theory for a multiple testing adjustment to a significance level of 0.05. Positive t values (red, yellow) indicate thicker cortical thickness. The p value for clusters indicates significant p values with the lightest blue color. Covariates included age, sex, body mass index, total triglycerides, APOE ε4 status, years of education, and intracranial volume.

Figure 4

Figure 4. Association of PC3 and PC5 with A/T/N/V biomarkers for Alzheimer disease in the APOE ε4 carrier group

A series of 14 separate post hoc linear regressions were used to assess the association of 7 amyloid, tau, neurodegeneration, and cerebrovascular disease (A/T/N/V) biomarkers with principal component (PC) 3 and PC5 in APOE ε4 carriers. Bonferroni adjustment was used to correct for the 14 association analyses between PC3, PC5, and 7 A/T/N/V endophenotypes. Covariates included age, sex, body mass index, total triglycerides, and APOE ε4 carrier status for all A/T/N/V phenotypes. For MRI biomarkers, we also included years of education and intracranial volume as additional covariates. The y-axis colors represent standardized β values from the linear regression analysis, with shades of red indicating a positive standardized β value and gray scale indicating a negative standardized β value. Aβ = β-amyloid1-42 peptide; FDG global cortex = cortical glucose standardized uptake value ratio measured from [18F]fluorodeoxyglucose-PET scans; p-tau = tau phosphorylated at threonine 181; t-tau = total tau; WMHI = white matter hyperintensity total volume. #p = 0.0537, *p < 0.05, **p < 0.01, ***p < 0.001.

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