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

被引:69
作者
Bernath, Megan M. [1 ,2 ,3 ,4 ]
Bhattacharyya, Sudeepa [5 ]
Nho, Kwangsik [1 ,2 ]
Barupal, Dinesh Kumar [6 ,7 ]
Fiehn, Oliver [7 ]
Baillie, Rebecca [8 ]
Risacher, Shannon L. [1 ,2 ]
Arnold, Matthias [9 ,12 ]
Jacobson, Tanner [1 ,2 ,3 ]
Trojanowski, John Q. [10 ]
Shaw, Leslie M. [10 ]
Weiner, Michael W. [11 ]
Doraiswamy, P. Murali [12 ]
Kaddurah-Daouk, Rima [12 ,13 ,14 ]
Saykin, Andrew J. [1 ,2 ,3 ]
机构
[1] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Indianapolis, IN 46202 USA
[2] Indiana Univ Sch Med, Ctr Neuroimaging, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA
[3] Indiana Univ Sch Med, Med & Mol Genet Dept, Indianapolis, IN 46202 USA
[4] Indiana Univ Sch Med, Med Scientist Training Program, Indianapolis, IN 46202 USA
[5] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA
[6] Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA
[7] Univ Calif Davis, NIH West Coast Metabol Ctr, Davis, CA USA
[8] Rosa & Co LLC, San Carlos, CA USA
[9] Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol, German Res Ctr Environm Hlth, Neuherberg, Germany
[10] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA
[11] Univ Calif San Francisco, Dept Radiol, Ctr Imaging Neurodegenerat Dis, San Francisco VA Med Ctr, San Francisco, CA 94143 USA
[12] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA
[13] Duke Univ, Duke Inst Brain Sci, Durham, NC USA
[14] Duke Univ, Dept Med, Durham, NC USA
基金
加拿大健康研究院;
关键词
POLYUNSATURATED FATTY-ACIDS; MILD COGNITIVE IMPAIRMENT; SURFACE-BASED ANALYSIS; AMYLOID-BETA; INITIATIVE ADNI; COMPOSITE SCORE; GUT MICROBIOTA; APOE GENOTYPE; BRAIN; PLASMA;
D O I
10.1212/WNL.0000000000009436
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:E2088 / E2098
页数:11
相关论文
共 50 条
[1]   The gut microbiota as an environmental factor that regulates fat storage [J].
Bäckhed, F ;
Ding, H ;
Wang, T ;
Hooper, LV ;
Koh, GY ;
Nagy, A ;
Semenkovich, CF ;
Gordon, JI .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (44) :15718-15723
[2]   Host-bacterial mutualism in the human intestine [J].
Bäckhed, F ;
Ley, RE ;
Sonnenburg, JL ;
Peterson, DA ;
Gordon, JI .
SCIENCE, 2005, 307 (5717) :1915-1920
[3]   Triglycerides cross the blood-brain barrier and induce central leptin and insulin receptor resistance [J].
Banks, W. A. ;
Farr, S. A. ;
Salameh, T. S. ;
Niehoff, M. L. ;
Rhea, E. M. ;
Morley, J. E. ;
Hanson, A. J. ;
Hansen, K. M. ;
Craft, S. .
INTERNATIONAL JOURNAL OF OBESITY, 2018, 42 (03) :391-397
[4]   Generation and quality control of lipidomics data for the alzheimer's disease neuroimaging initiative cohort [J].
Barupal, Dinesh Kumar ;
Fan, Sili ;
Wancewicz, Benjamin ;
Cajka, Tomas ;
Sa, Michael ;
Showalter, Megan R. ;
Baillie, Rebecca ;
Tenenbaum, Jessica D. ;
Louie, Gregory ;
Kaddurah-Daouk, Rima ;
Fiehn, Oliver .
SCIENTIFIC DATA, 2018, 5
[5]   THE PECKING ORDER OF FREE-RADICALS AND ANTIOXIDANTS - LIPID-PEROXIDATION, ALPHA-TOCOPHEROL, AND ASCORBATE [J].
BUETTNER, GR .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1993, 300 (02) :535-543
[6]   Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer's disease mouse models with abundant Aβ in plasma [J].
Burgess, Braydon L. ;
McIsaac, Sean A. ;
Naus, Kathryn E. ;
Chan, Jeniffer Y. ;
Tansley, Gavin H. K. ;
Yang, Jing ;
Miao, Fudan ;
Ross, Colin J. D. ;
van Eck, Miranda ;
Hayden, Michael R. ;
van Nostrand, William ;
St. George-Hyslop, Peter ;
Westaway, David ;
Wellington, Cheryl L. .
NEUROBIOLOGY OF DISEASE, 2006, 24 (01) :114-127
[7]  
Cajka T, 2017, METHODS MOL BIOL, V1609, P149, DOI 10.1007/978-1-4939-6996-8_14
[8]   Longitudinal Changes in White Matter Disease and Cognition in the First Year of the Alzheimer Disease Neuroimaging Initiative [J].
Carmichael, Owen ;
Schwarz, Christopher ;
Drucker, David ;
Fletcher, Evan ;
Harvey, Danielle ;
Beckett, Laurel ;
Jack, Clifford R. ;
Weiner, Michael ;
DeCarli, Charles .
ARCHIVES OF NEUROLOGY, 2010, 67 (11) :1370-1378
[9]   Interactions between age and apoE genotype on fasting and postprandial triglycerides levels [J].
Carvalho-Wells, Andrew L. ;
Jackson, Kim G. ;
Gill, Rosalynn ;
Olano-Martin, Estibaliz ;
Lovegrove, Julie A. ;
Williams, Christine M. ;
Minihane, Anne M. .
ATHEROSCLEROSIS, 2010, 212 (02) :481-487
[10]   Association Between Serum Triglycerides and Cerebral Amyloidosis in Cognitively Normal Elderly [J].
Choi, Hyo Jung ;
Byun, Min Soo ;
Yi, Dahyun ;
Choe, Young Min ;
Sohn, Bo Kyung ;
Baek, Hye Won ;
Lee, Jun Ho ;
Kim, Hyun Jung ;
Han, Ji Young ;
Yoon, Eun Jin ;
Kim, Yu Kyeong ;
Woo, Jong Inn ;
Lee, Dong Young .
AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY, 2016, 24 (08) :604-612