Multiomics analysis to explore blood metabolite biomarkers in an Alzheimer’s Disease Neuroimaging Initiative cohort

作者：Takaki Oka, Yuki Matsuzawa, Momoka Tsuneyoshi, Yoshitaka Nakamura, Ken Aoshima, Hiroshi Tsugawa, Michael Walter Weiner, Paul S. S. Aisen, Ronald Petersen, Clifford R. Jack, William J. Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel A. Beckett, Robert C. Green, Andrew J. Saykin, John C. Morris, Leslie M. Shaw, Enchi Liu, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah J. Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Danielle Jenine Harvey, Michael Donohue, Matt A. Bernstein, Nick C. Fox, Paul M. Thompson, Norbert W. Schuff, Charles DeCarli, Bret Borowski, Jeff L. Gunter, Matthew L. Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan M. Landau, Nigel J. Cairns, Erin Householder, Lisa Taylor‐Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen L. Crawford, Scott Neu, Tatiana Foroud, Steven Potkin, Li Shen, Kelley M. Faber, Sungeun Kim, Kwangsik T. Nho, Zaven Kachaturian, Richard A. Frank, Peter Jeffrey Snyder, Susan E. Molchan, JEFFREY A. KAYE, Joseph F. Quinn, Betty Lind, Raina Carter, Sara Dolen, Lon S. S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M. Spann, James B. Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Ronald Petersen, Sara S. Mason, Colleen S. Albers, David S. Knopman, Kris Johnson, Rachelle Smith Doody, Javier Villanueva Meyer, Munir H. Chowdhury, Susan D. Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau M. Ances, John C. Morris, Maria B. Carroll, Sue Leon, Erin Householder, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel C. Marson, Randall Griffith, David Clark, David Geldmacher, John C. Brockington, Erik D. Roberson, Hillel T. Grossman, Effie M. Mitsis, Leyla de Toledo‐Morrell, Raj C. Shah, Ranjan Duara, Daniel Varón, Maria T. Greig, Peggy Roberts, Marilyn Albert, Chiadi U. Onyike, Daniel D’Agostino, Stephanie Kielb, James E. Galvin, Dana M. Pogorelec, Brittany Cerbone, Christina A. Michel, Henry Rusinek, Mony J. de Leon, Lidia Glodzik, Susan De Santi, Pudugramam Murali Doraiswamy, Jeffrey R. Petrella, Terence Z. Wong, Steven Edward Arnold, Jason H. Karlawish, David A. Wolk, Charles David Smith, Gregory A. Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. López, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Ruth A. Mulnard, Gaby T. Thai, Catherine Mc Adams Ortiz, Kyle B. Womack, Dana Mathews, Mary Ellen Quiceno, Ramon Diaz Arrastia, Richard King, Myron Weiner, Kristen Martin Cook, Michael D. Devous, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey Murray Burns, Heather S. Anderson, Russell Howard Swerdlow, Liana G. Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R. Graff Radford, Francine C. Parfitt, Tracy Kendall, Heather K. Johnson, Martin Rhys Farlow, Ann Marie Hake, Brandy R. Matthews, Scott Herring, Cynthia Hunt, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra E. Black, Bojana Stefanovic, Curtis Caldwell, Ging‐Yuek Robin Hsiung, Howard Feldman, Benita Mudge, Michele Assaly, Andrew Kertesz, John Rogers, Dick Trost, Charles B. Bernick, Donna Munic, Diana R. Kerwin, Marek-Marsel Mesulam, Kristine Lipowski, Chuang Kuo Wu, Nancy Ainsworth Johnson, Carl Sadowsky, Walter Fabián Martínez, Teresa Villena, Raymond Scott Turner, Kathleen B. Johnson, Brigid Reynolds, Reisa Anne Sperling, Keith A. Johnson, Gad A. Marshall, Meghan T Frey, Jerome Albert Yesavage, Joy L. Taylor, Barton Lane, Allyson C Rosen, Jared R. Tinklenberg, Marwan Noel Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil W. Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas Olabode Obisesan, Saba Wolday, Joanne S. Allard, Alan Jay Lerner, Paula K. Ogrocki, Leon Hudson, Evan M. Fletcher, Owen Thomas Carmichael, John Olichney, Charles DeCarli, Smita Kittur, MICHAEL J. BORRIE, T. Y. Lee, Robert Bartha, Sterling C. Johnson, Sanjay Asthana, Cynthia M. Carlsson, Steven G. Potkin, Adrian Preda, Dana R. Nguyen, Pierre N. Tariot, Adam Fleisher, Stephanie Reeder, Vernice E. Bates, Horacio A. Capote, Michelle M. Rainka, Douglas W. Scharre, Maria Kataki, Anahita Adeli, Earl A. Zimmerman, Dzintra F. Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Robert B. Santulli, Tamar J. Kitzmiller, Eben S. Schwartz, Kaycee M. Sink, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Henry W. Querfurth, Geoffrey N. Tremont, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce Leonard Miller, Jacobo E Mintzer, KENNETH M. SPICER, David Bachman, Elizabeth C. Finger, Stephen Pasternak, Irina Rachinsky, John Rogers, Andrew Kertesz, Dick J. Drost, Nunzio Pomara, Raymundo T. Hernando, Antero Sarrael, Susan K. Schultz, Laura L. Boles Ponto, Hyungsub Shim, Karen E. L. Smith, Norman R. Relkin, Gloria Chaing, Lisa Raudin, Amanda Elizabeth Smith, Kristin Fargher, Balebail Ashok Raj · 发表于：Scientific Reports · 年份：2024 · DOI：10.1038/s41598-024-56837-1 · 被引用次数：34 · 研究领域：Metabolomics and Mass Spectrometry Studies、Alzheimer's disease research and treatments、Tryptophan and brain disorders

Abstract Alzheimer's disease (AD) is a neurodegenerative disease that commonly causes dementia. Identifying biomarkers for the early detection of AD is an emerging need, as brain dysfunction begins two decades before the onset of clinical symptoms. To this end, we reanalyzed untargeted metabolomic mass spectrometry data from 905 patients enrolled in the AD Neuroimaging Initiative (ADNI) cohort using MS-DIAL, with 1,304,633 spectra of 39,108 unique biomolecules. Metabolic profiles of 93 hydrophilic metabolites were determined. Additionally, we integrated targeted lipidomic data (4873 samples from 1524 patients) to explore candidate biomarkers for predicting progressive mild cognitive impairment (pMCI) in patients diagnosed with AD within two years using the baseline metabolome. Patients with lower ergothioneine levels had a 12% higher rate of AD progression with the significance of P = 0.012 (Wald test). Furthermore, an increase in ganglioside (GM3) and decrease in plasmalogen lipids, many of which are associated with apolipoprotein E polymorphism, were confirmed in AD patients, and the higher levels of lysophosphatidylcholine (18:1) and GM3 d18:1/20:0 showed 19% and 17% higher rates of AD progression, respectively (Wald test: P = 3.9 × 10 –8 and 4.3 × 10 –7 ). Palmitoleamide, oleamide, diacylglycerols, and ether lipids were also identified as significantly altered metabolites at baseline in patients with pMCI. The integrated analysis of metabolites and genomics data showed th...