Dissociation of tau pathology and neuronal hypometabolism within the ATN framework of Alzheimer’s disease

• DOI: 10.1038/s41467-022-28941-1
• Publication Date: 2022-03-21T11:03:30Z
• Authors: Michael Tran Duong; Sandhitsu R. Das; Xueying Lyu; Long Xie; Hayley Richardson; Sharon X. Xie; Paul A. Yushkevich; ; Michael Weiner; Paul Aisen; Ronald Petersen; Clifford R. Jack; William Jagust; John Q. Trojanowki; Arthur W. Toga; Laurel Beckett; Robert C. Green; Andrew J. Saykin; John C. Morris; Leslie M. Shaw; Enchi Liu; Tom Montine; Ronald G. Thomas; Michael Donohue; Sarah Walter; Devon Gessert; Tamie Sather; Gustavo Jimenez-M...; Danielle Harvey; Matthew Bernstein; Nick Fox; Paul Thompson; Norbert Schuff; Charles DeCarli; Bret Borowski; Jeff Gunter; Matt Senjem; Prashanthi Vemuri; David Jones; Kejal Kantarci; Chad Ward; Robert A. Koeppe; Norm Foster; Eric M. Reiman; Kewei Chen; Chet Mathis; Susan Landau; Nigel J. Cairns; Erin Householder; Lisa Taylor-Reinwald; Virginia M-Y Lee; Magdalena Korecka; Michal Figurski; Karen Crawford; Scott Neu; Tatiana M. Foroud; Li Shen; Kelley Faber; Sungeun Kim; Kwangsik Nho; Zaven Khachaturian; Richard Frank; Peter J. Snyder; Susan Molchan; Jeffrey Kaye; Joseph Quinn; Betty Lind; Raina Carter; Sara Dolen; Lon S. Schneider; Sonia Pawluczyk; Mauricio Beccera; Liberty Teodoro; Bryan M. Spann; James Brewer; Helen Vanderswag; Adam Fleisher; Judith L. Heidebrink; Joanne L. Lord; Sara S. Mason; Colleen S. Albers; David Knopman; Kris Johnson; Rachelle S. Doody; Javier Villanueva...; Munir Chowdhury; Susan Rountree; Mimi Dang; Yaakov Stern; Lawrence S. Honig; Karen L. Bell; Beau Ances; Maria Carroll; Sue Leon; Mark A. Mintun; Stacy Schneider; Angela Oliver; Randall Griffith; David Clark; David Geldmacher; John Brockington; Erik Roberson; Hillel Grossman; Effie Mitsis; Leyla deToledo-Mo...; Raj C. Shah; Ranjan Duara; Daniel Varon; Maria T. Greig; Peggy Roberts; Marilyn Albert; Chiadi 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; P. Murali Doraiswamy; Jeffrey R. Petrella; Terence Z. Wong; Christopher M. Clark; Steven E. Arnold; Jason H. Karlawish; David A. Wolk; Charles D. Smith; Gregory Jicha; Peter Hardy; Partha Sinha; Elizabeth Oates; Gary Conrad; Oscar L. Lopez; MaryAnn Oakley; Donna M. Simpson; Anton P. Porstein...; Bonnie S. Goldstein; Kim Martin; Kelly M. Makino; M. Saleem Ismail; Connie Brand; Ruth A. Mulnard; Gaby Thai; Catherine McAdams...; Kyle Womack; Dana Mathews; Mary Quiceno; Ramon Diaz-Arrastia; Richard King; Myron Weiner; Kristen Martin Cook; Michael Devous; Allan I. Levey; James J. Lah; Janet S. Cellar; Jeffrey M. Burns; Heather S. Anderson; Russell H. Swerdlow; Liana Apostolova; Kathleen Tingus; Ellen Woo; Daniel H. S. Silv...; Po H. Lu; George Bartzokis; Neill R. Graff-Ra...; Francine Parfitt; Tracy Kendall; Heather Johnson; Martin R. Farlow; Ann Marie Hake; Brandy R. Matthews; Scott Herring; Cynthia Hunt; Christopher H. va...; Richard E. Carson; Martha G. MacAvoy; Howard Chertkow; Howard Bergman; Chris Hosein; Sandra Black; Bojana Stefanovic; Curtis Caldwell; Ging-Yuek Robin H...; Howard Feldman; Benita Mudge; Michele Assaly; Andrew Kertesz; John Rogers; Charles Bernick; Donna Munic; Diana Kerwin; Marek Marsel Mesulam; Kristine Lipowski; Chuang-Kuo Wu; Nancy Johnson; Carl Sadowsky; Walter Martinez; Teresa Villena; Raymond Scott Turner; Kathleen Johnson; Brigid Reynolds; Reisa A. Sperling; Keith A. Johnson; Gad Marshall; Meghan Frey; Jerome Yesavage; Joy L. Taylor; Barton Lane; Allyson Rosen; Jared Tinklenberg; Marwan N. Sabbagh; Christine M. Belden; Sandra A. Jacobson; Sherye A. Sirrel; Neil Kowall; Ronald Killiany; Andrew E. Budson; Alexander Norbash; Patricia Lynn Joh...; Thomas O. Obisesan; Saba Wolday; Joanne Allard; Alan Lerner; Paula Ogrocki; Leon Hudson; Evan Fletcher; Owen Carmichael; John Olichney; Smita Kittur; Michael Borrie; T.-Y. Lee; Rob Bartha; Sterling Johnson; Sanjay Asthana; Cynthia M. Carlsson; Steven G. Potkin; Adrian Preda; Dana Nguyen; Pierre Tariot; Stephanie Reeder; Vernice Bates; Horacio Capote; Michelle Rainka; Douglas W. Scharre; Maria Kataki; Anahita Adeli; Earl A. Zimmerman; Dzintra 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 Querfurth; Geoffrey Tremont; Stephen Salloway; Paul Malloy; Stephen Correia; Howard J. Rosen; Bruce L. Miller; Jacobo Mintzer; Kenneth Spicer; David Bachman; Elizabether Finger; Stephen Pasternak; Irina Rachinsky; Dick Drost; Nunzio Pomara; Raymundo Hernando; Antero Sarrael; Susan K. Schultz; Laura L. Boles Ponto; Hyungsub Shim; Karen Ekstam Smith; Norman Relkin; Gloria Chiang; Lisa Ravdin; Amanda Smith; Kristin Fargher; Balebail Ashok Raj; David A. Wolk; Ilya M. Nasrallah
• Keywords: Tau Pathology

Abstract Alzheimer’s disease (AD) is defined by amyloid (A) and tau (T) pathologies, with T better correlated to neurodegeneration (N). However, N have complex regional relationships in part related non-AD factors that influence N. With machine learning, we assessed heterogeneity 18 F-flortaucipir vs. F-fluorodeoxyglucose positron emission tomography as markers of neuronal hypometabolism (N M ) 289 symptomatic patients from the Disease Neuroimaging Initiative. We identified six T/N clusters differing limbic cortical patterns. The canonical group was pattern lowest regression residuals. Groups resilient had less than expected relative displayed cognition group. susceptible more given exhibited worse cognitive decline, imaging clinical measures concordant copathologies. Together, mismatch reveals distinct signatures pathobiological prognostic implications for AD.