Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers

被引：192

作者：

Nho, Kwangsik ^{[1
,2
]}

Kueider-Paisley, Alexandra ^{[3
]}

MahmoudianDehkordi, Siamak ^{[3
]}

Arnold, Matthias ^{[3
,4
]}

Risacher, Shannon L. ^{[1
,2
]}

Louie, Gregory ^{[3
]}

Blach, Colette ^{[5
]}

Baillie, Rebecca ^{[6
]}

Han, Xianlin ^{[7
]}

Kastenmueller, Gabi ^{[4
,8
]}

Jia, Wei ^{[9
]}

Xie, Guoxiang ^{[9
]}

Ahmad, Shahzad ^{[10
]}

Hankemeier, Thomas ^{[11
]}

van Duijn, Cornelia M. ^{[10
]}

Trojanowski, John Q. ^{[12
]}

Shaw, Leslie M. ^{[12
]}

Weiner, Michael W. ^{[13
]}

Doraiswamy, P. Murali ^{[3
,14
,15
]}

Saykin, Andrew J. ^{[1
,2
]}

Kaddurah-Daouk, Rima ^{[3
,14
,15
]}

Aisen, Paul ^{[17
]}

Weiner, Michael ^{[18
,101
]}

Petersen, Ronald ^{[19
]}

Jack, Clifford R., Jr. ^{[19
]}

Jagust, William ^{[16
,20
]}

Trojanowki, John Q. ^{[21
,46
,103
]}

Toga, Arthur W. ^{[17
,22
]}

Beckett, Laurel ^{[23
]}

Green, Robert C. ^{[24
,100
]}

Morris, John ^{[26
]}

Khachaturian, Zaven ^{[27
]}

Sorensen, Greg ^{[28
]}

Carrillo, Maria ^{[29
]}

Kuller, Lew ^{[30
]}

Raichle, Marc ^{[26
]}

Paul, Steven ^{[31
]}

Davies, Peter ^{[32
]}

Fillit, Howard ^{[33
]}

Hefti, Franz ^{[34
]}

Holtzman, David ^{[26
,35
]}

Mesulam, M. Marcel ^{[35
]}

Potter, William ^{[36
]}

Snyder, Peter ^{[37
]}

Montine, Tom ^{[38
]}

Jimenez, Gustavo ^{[22
]}

Donohue, Michael ^{[22
,39
]}

Gessert, Devon ^{[22
]}

Harless, Kelly ^{[22
]}

Salazar, Jennifer ^{[22
]}

机构：

[1] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA

[2] Indiana Univ Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA

[3] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27708 USA

[4] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol, Neuherberg, Germany

[5] Duke Univ, Duke Mol Physiol Inst, Durham, NC USA

[6] Rosa & Co LLC, San Carlos, CA USA

[7] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA

[8] German Ctr Diabet Res DZD, Neuherberg, Germany

[9] Univ Hawaii, Canc Ctr, Honolulu, HI 96822 USA

[10] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[11] Leiden Univ, Leiden Acad Ctr Drug Res, Div Analyt Biosci, Leiden, Netherlands

[12] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA

[13] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Radiol, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94143 USA

[14] Duke Univ, Duke Inst Brain Sci, Durham, NC 27708 USA

[15] Duke Univ, Dept Med, Durham, NC 27708 USA

[16] Univ Calif San Francisco, San Francisco, CA 94143 USA

[17] Univ Southern Calif, Los Angeles, CA USA

[18] UC San Francisco, San Francisco, CA USA

[19] Mayo Clin, Rochester, MN USA

[20] Univ Calif Berkeley, Berkeley, CA USA

[21] Univ Penn, Philadelphia, PA 19104 USA

[22] USC, Los Angeles, CA USA

[23] Univ Calif Davis, Davis, CA USA

[24] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA

[25] Indiana Univ, Bloomington, IN 47405 USA

[26] Washington Univ, St Louis, MO USA

[27] Prevent Alzheimers Dis 2020, Rockville, MD USA

[28] Siemens AG, Washington, DC USA

[29] Alzheimers Assoc, Chicago, IL USA

[30] Univ Pittsburgh, Pittsburgh, PA 15260 USA

[31] Cornell Univ, Ithaca, NY 14853 USA

[32] Yeshiva Univ, Albert Einstein Coll Med, New York, NY 10033 USA

[33] AD Drug Discovery Fdn, New York, NY USA

[34] Acumen Pharmaceut, Livermore, CA USA

[35] Northwestern Univ, Evanston, IL 60208 USA

[36] NIMH, Bethesda, MD 20892 USA

[37] Brown Univ, Providence, RI 02912 USA

[38] Univ Washington, Seattle, WA 98195 USA

[39] Univ Calif San Diego, San Diego, CA USA

[40] Univ London, London, England

[41] UCLA, Sch Med, Los Angeles, CA USA

[42] UCSF, MRI, San Francisco, CA USA

[43] Univ Michigan, Ann Arbor, MI 48109 USA

[44] Univ Utah, Salt Lake City, UT 84112 USA

[45] Banner Alzheimers Inst, Phoenix, AZ USA

[46] UPenn Sch Med, Philadelphia, PA USA

[47] UC Irvine, Irvine, CA USA

[48] NIA, Bethesda, MD 20892 USA

[49] Johns Hopkins Univ, Baltimore, MD 21218 USA

[50] Oregon Hlth & Sci Univ, Portland, OR 97201 USA

来源：

ALZHEIMERS & DEMENTIA | 2019年 / 15卷 / 02期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

Metabolomics; Bile acid; Alzheimer's disease; Amyloid-beta; CSF biomarkers; Brain glucose metabolism; PET; MRI; Gut-liver-brain axis; ISOLATED RAT HEPATOCYTES; SURFACE-BASED ANALYSIS; GUT-BRAIN AXIS; CEREBROSPINAL-FLUID; CHOLESTEROL-METABOLISM; URSODEOXYCHOLIC ACID; OXIDATIVE STRESS; RANDOM-FIELD; VITAMIN-D; FDG-PET;

D O I：

10.1016/j.jalz.2018.08.012

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Introduction: Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer's disease (AD) including neuroinflammation and amyloid-beta deposition. Method: Serum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n = 1562) were measured using targeted metabolomic profiling. We assessed the association of BAs with the "A/T/N" (amyloid, tau, and neurodegeneration) biomarkers for AD: cerebrospinal fluid (CSF) biomarkers, atrophy (magnetic resonance imaging), and brain glucose metabolism ([F-18]FDG PET). Results: Of 23 BAs and relevant calculated ratios after quality control procedures, three BA signatures were associated with CSFA beta(1-42) ("A") and three with CSF p-tau181 ("T") (corrected P < .05). Furthermore, three, twelve, and fourteen BA signatures were associated with CSF t-tau, glucose metabolism, and atrophy ("N"), respectively (corrected P < .05). Discussion: This is the first study to show serum-based BA metabolites are associated with "A/T/N" AD biomarkers, providing further support for a role of BA pathways in AD pathophysiology. Prospective clinical observations and validation in model systems are needed to assess causality and specific mechanisms underlying this association. (C) 2018 Published by Elsevier Inc. on behalf of the Alzheimer's Association.

引用

页码：232 / 244

页数：13

共 50 条

[11] Imaging and Biomarkers in Early Alzheimer's Disease and Mild Cognitive Impairment
Petersen, R. C.
Jack, C. R., Jr.
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2009, 86 (04) : 438 - 441
[12] CSF Biomarkers in Prediction of Cerebral and Clinical Change in Mild Cognitive Impairment and Alzheimer's Disease
Fjell, Anders M.
Walhovd, Kristine B.
Fennema-Notestine, Christine
McEvoy, Linda K.
Hagler, Donald J.
Holland, Dominic
Brewer, James B.
Dale, Anders M.
JOURNAL OF NEUROSCIENCE, 2010, 30 (06) : 2088 - 2101
[13] Biomarkers of mild cognitive impairment and Alzheimer's disease
Tang, Bor Luen
Kumar, Rajeev
ANNALS ACADEMY OF MEDICINE SINGAPORE, 2008, 37 (05) : 406 - 410
[14] Disease progression model in subjects with mild cognitive impairment from the Alzheimer's disease neuroimaging initiative: CSF biomarkers predict population subtypes
Samtani, Mahesh N.
Raghavan, Nandini
Shi, Yingqi
Novak, Gerald
Farnum, Michael
Lobanov, Victor
Schultz, Tim
Yang, Eric
DiBernardo, Allitia
Narayan, Vaibhav A.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2013, 75 (01) : 146 - 161
[15] Multimodal classification of Alzheimer's disease and mild cognitive impairment
Zhang, Daoqiang
Wang, Yaping
Zhou, Luping
Yuan, Hong
Shen, Dinggang
NEUROIMAGE, 2011, 55 (03) : 856 - 867
[16] Identification of Altered Metabolic Pathways in Plasma and CSF in Mild Cognitive Impairment and Alzheimer's Disease Using Metabolomics
Trushina, Eugenia
Dutta, Tumpa
Persson, Xuan-Mai T.
Mielke, Michelle M.
Petersen, Ronald C.
PLOS ONE, 2013, 8 (06):
[17] CSF biomarkers for mild cognitive impairment
Blennow, K
JOURNAL OF INTERNAL MEDICINE, 2004, 256 (03) : 224 - 234
[18] Depressive symptoms and CSF Alzheimer's disease biomarkers in relation to clinical symptom onset of mild cognitive impairment
Chan, Carol K.
Soldan, Anja
Pettigrew, Corinne
Wang, Jiangxia
Albert, Marilyn
Rosenberg, Paul B.
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING, 2020, 12 (01)
[19] Improved multimodal biomarkers for Alzheimer's disease and Mild Cognitive Impairment diagnosis - data from ADNI
Martinez-Torteya, Antonio
Trevino-Alvarado, Victor
Tamez-Pena, Jose
MEDICAL IMAGING 2013: COMPUTER-AIDED DIAGNOSIS, 2013, 8670
[20] Biomarkers of Alzheimer's Disease in the Cerebrospinal Fluid of Spanish Patients With Mild Cognitive Impairment
Monge-Argiles, J. A.
Munoz-Ruiz, C.
Pampliega-Perez, A.
Gomez-Lopez, M. J.
Sanchez-Paya, J.
Borja, E. Rodriguez
Ruiz-Vegara, M.
Montoya-Gutierrez, F. J.
Leiva-Santana, C.
NEUROCHEMICAL RESEARCH, 2011, 36 (06) : 986 - 993

← 1 2 3 4 5 →