Tau‐Atrophy Variability Reveals Phenotypic Heterogeneity in Alzheimer's Disease. Issue 5 (15th October 2021)

• Record Type: Journal Article
• Authors: Das, Sandhitsu R.; Lyu, Xueying; Duong, Michael Tran; Xie, Long; McCollum, Lauren; de Flores, Robin; DiCalogero, Michael; Irwin, David J.; Dickerson, Bradford C.; Nasrallah, Ilya M.; Yushkevich, Paul A.; Wolk, David A.
• Other Names: Weiner Michael investigator.; Aisen Paul investigator.; Petersen Ronald investigator.; Jack Clifford R. investigator.; Jagust William investigator.; Trojanowki John Q. investigator.; Toga Arthur W. investigator.; Beckett Laurel investigator.; Green Robert C. investigator.; Saykin Andrew J. investigator.; Morris John investigator.; Shaw Leslie M. investigator.; Liu Enchi investigator.; Montine Tom investigator.; Thomas Ronald G. investigator.; Donohue Michael investigator.; Walter Sarah investigator.; Gessert Devon investigator.; Sather Tamie investigator.; Jiminez Gus investigator.; Harvey Danielle investigator.; Donohue Michael investigator.; Bernstein Matthew investigator.; Fox Nick investigator.; Thompson Paul investigator.; Schuff Norbert investigator.; DeCArli Charles investigator.; Borowski Bret investigator.; Gunter Jeff investigator.; Senjem Matt investigator.; Vemuri Prashanthi investigator.; Jones David investigator.; Kantarci Kejal investigator.; Ward Chad investigator.; Koeppe Robert A. investigator.; Foster Norm investigator.; Reiman Eric M. investigator.; Chen Kewei investigator.; Mathis Chet investigator.; Landau Susan investigator.; Cairns Nigel J. investigator.; Householder Erin investigator.; Reinwald Lisa Taylor investigator.; Lee Virginia investigator.; Korecka Magdalena investigator.; Figurski Michal investigator.; Crawford Karen investigator.; Neu Scott investigator.; Foroud Tatiana M. investigator.; Potkin Steven investigator.; Shen Li investigator.; Kelley Faber investigator.; Kim Sungeun investigator.; Nho Kwangsik investigator.; Kachaturian Zaven investigator.; Frank Richard investigator.; Snyder Peter J. investigator.; Molchan Susan investigator.; Kaye Jeffrey investigator.; Quinn Joseph investigator.; Lind Betty investigator.; Carter Raina investigator.; Dolen Sara investigator.; Schneider Lon S. investigator.; Pawluczyk Sonia investigator.; Beccera Mauricio investigator.; Teodoro Liberty investigator.; Spann Bryan M. investigator.; Brewer James investigator.; Vanderswag Helen investigator.; Fleisher Adam investigator.; Heidebrink Judith L. investigator.; Lord Joanne L. investigator.; Petersen Ronald investigator.; Mason Sara S. investigator.; Albers Colleen S. investigator.; Knopman David investigator.; Johnson Kris investigator.; Doody Rachelle S. investigator.; Meyer Javier Villanueva investigator.; Chowdhury Munir investigator.; Rountree Susan investigator.; Dang Mimi investigator.; Stern Yaakov investigator.; Honig Lawrence S. investigator.; Bell Karen L. investigator.; Ances Beau investigator.; Morris John C. investigator.; Carroll Maria investigator.; Leon Sue investigator.; Householder Erin investigator.; Mintun Mark A. investigator.; Schneider Stacy investigator.; Oliver Angela investigator.; Marson Daniel investigator.; Griffith Randall investigator.; Clark David investigator.; Geld‐Macher David investigator.; Brockington John investigator.; Roberson Erik investigator.; Grossman Hillel investigator.; Mitsis Effie investigator.; de Toledo‐Morrell Leyla investigator.; Shah Raj C. investigator.; Duara Ranjan investigator.; Varon Daniel investigator.; Greig Maria T. investigator.; Roberts Peggy investigator.; Albert Marilyn investigator.; Onyike Chiadi investigator.; D'Agostino Daniel investigator.; Kielb Stephanie investigator.; Galvin James E. investigator.; Pogorelec Dana M. investigator.; Cerbone Brittany investigator.; Michel Christina A. investigator.; Rusinek Henry investigator.; de Leon Mony J investigator.; Glodzik Lidia investigator.; De Santi Susan investigator.; Doraiswamy P. Murali investigator.; Petrella Jeffrey R. investigator.; Wong Terence Z. investigator.; Arnold Steven E. investigator.; Karlawish Jason H. investigator.; Wolk David investigator.; Smith Charles D. investigator.; Jicha Greg investigator.; Hardy Peter investigator.; Sinha Partha investigator.; Oates Elizabeth investigator.; Conrad Gary investigator.; Lopez Oscar L. investigator.; Oakley MaryAnn investigator.; Simpson Donna M. investigator.; Porsteinsson Anton P. investigator.; Goldstein Bonnie S. investigator.; Martin Kim investigator.; Makino Kelly M. investigator.; Ismail M. Saleem investigator.; Brand Connie investigator.; Mulnard Ruth A. investigator.; Thai Gaby investigator.; Ortiz Catherine Mc Adams investigator.; Womack Kyle investigator.; Mathers Dana investigator.; Quiceno Mary investigator.; Arrastia Ramon Diaz investigator.; King Richard investigator.; Weiner Myron investigator.; Martin Cook Kristen investigator.; DeVous Michael investigator.; Levey Allan I. investigator.; Lah James J. investigator.; Cellar Janet S. investigator.; Bums Jeffrey M. investigator.; Anderson Heather S. investigator.; Swerdlow Russell H. investigator.; Apostolova Liana investigator.; Tingus Kathleen investigator.; Woo Ellen investigator.; Silverman Daniel H.S. investigator.; Lu Po H. investigator.; Bartzokis George investigator.; Graff Radford Neill R investigator.; Parfitt Francine investigator.; Kendall Tracy investigator.; Johnson Heather investigator.; Farlow Martin R. investigator.; Hake Ann Marie investigator.; Matthews Brandy R. investigator.; Herring Scott investigator.; Hunt Cynthia investigator.; van Dyck Christopher H. investigator.; Carson Richard E. investigator.; MacAvoy Martha G. investigator.; Chertkow Howard investigator.; Bergman Howard investigator.; Hosein Chris investigator.; Black Sandra investigator.; Stefanovic Bojana investigator.; Caldwell Curtis investigator.; Hsiung Ging Yuek Robin investigator.; Feldman Howard investigator.; Mudge Benita investigator.; Assaly Michele investigator.; Kertesz Andrew investigator.; Rogers John investigator.; Trost Dick investigator.; Bernick Charles investigator.; Munic Donna investigator.; Kerwin Diana investigator.; Mesulam Marek Marsel investigator.; Lipowski Kristine investigator.; Wu Chuang Kuo investigator.; Johnson Nancy investigator.; Sadowsky Carl investigator.; Martinez Walter investigator.; Villena Teresa investigator.; Turner Raymond Scott investigator.; Kathleen Johnson NP investigator.; Brigid Reynolds NP investigator.; Sperling Reisa A. investigator.; Johnson Keith A. investigator.; Marshall Gad investigator.; Frey Meghan investigator.; Yesavage Jerome investigator.; Taylor Joy L. investigator.; Lane Barton investigator.; Rosen Allison investigator.; Tinklenberg Jared investigator.; Sabbagh Marwan N. investigator.; Belden Christine M. investigator.; Jacobson Sandra A. investigator.; Sirrel Sherye A. investigator.; Kowall Neil investigator.; Killiany Ronald investigator.; Budson Andrew E. investigator.; der Norbash Alexan investigator.; Johnson Patricia Lynn investigator.; Obisesan Thomas O. investigator.; Wolday Saba investigator.; Allard Joanne investigator.; Lerner Alan investigator.; Ogrocki Paula investigator.; Hudson Leon investigator.; Fletcher Evan investigator.; Carmichael Owen investigator.; Olichney John investigator.; DeCarli Charles investigator.; Kittur Smita investigator.; Borrie Michael investigator.; Lee T Y investigator.; Bartha Rob investigator.; Johnson Sterling investigator.; Asthana Sanjay investigator.; Carlsson Cynthia M. investigator.; Potkin Steven G. investigator.; Preda Adrian investigator.; Nguyen Dana investigator.; Tariot Pierre investigator.; Fleisher Adam investigator.; Reeder Stephanie investigator.; Bates Vemice investigator.; Capote Horacio investigator.; Rainka Michelle investigator.; Scharre Douglas W. investigator.; Kataki Maria investigator.; Adeli Anahita investigator.; Zimmerman Earl A. investigator.; Celmins Dzintra investigator.; Brown Alice D. investigator.; Pearlson Godfrey D. investigator.; Blank Karen investigator.; Anderson Karen investigator.; Santulli Robert B. investigator.; Kitzmiller Tamar J. investigator.; Schwartz Eben S. investigator.; Sink Kaycee M. investigator.; Williamson Jeff D. investigator.; Garg Pradeep investigator.; Watkins Franklin investigator.; Ott Brian R. investigator.; Querfurth Henry investigator.; Tremont Geoffrey investigator.; Salloway Stephen investigator.; Malloy Paul investigator.; Correia Stephen investigator.; Rosen Howard J. investigator.; Miller Bruce L. investigator.; Mintzer Jacobo investigator.; Spicer Kenneth investigator.; Bachman David investigator.; Finger Elizabether investigator.; Pasternak Stephen investigator.; Rachinsky Irina investigator.; Rogers John investigator.; Kertesz Andrew investigator.; Drost Dick investigator.; Pomara Nunzio investigator.; Hernando Raymundo investigator.; Sarrael Antero investigator.; Schultz Susan K. investigator.; Boles Ponto Laura L. investigator.; Shim Hyungsub investigator.; Smith Karen Elizabeth investigator.; Relkin Norman investigator.; Chaing Gloria investigator.; Raudin Lisa investigator.; Smith Amanda investigator.; Fargher Kristin investigator.; Raj Balebail Ashok investigator.;
• Is Part Of: Annals of neurology. Volume 90:Issue 5(2021)
• Page Start: 751
• Page End: 762
• Publication Date: 2021-10-15
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.26233
• Languages: English
• ISSNs: 0364-5134

Abstract

Abstract : Objective: Tau neurofibrillary tangles (T) are the primary driver of downstream neurodegeneration (N) and subsequent cognitive impairment in Alzheimer's disease (AD). However, there is substantial variability in the T‐N relationship – manifested in higher or lower atrophy than expected for level of tau in a given brain region. The goal of this study was to determine if region‐based quantitation of this variability allows for identification of underlying modulatory factors, including polypathology. Methods: Cortical thickness (N) and 18 F‐Flortaucipir SUVR (T) were computed in 104 gray matter regions from a cohort of cognitively‐impaired, amyloid‐positive (A+) individuals. Region‐specific residuals from a robust linear fit between SUVR and cortical thickness were computed as a surrogate for T‐N mismatch. A summary T‐N mismatch metric defined using residuals were correlated with demographic and imaging‐based modulatory factors, and to partition the cohort into data‐driven subgroups. Results: The summary T‐N mismatch metric correlated with underlying factors such as age and burden of white matter hyperintensity lesions. Data‐driven subgroups based on clustering of residuals appear to represent different biologically relevant phenotypes, with groups showing distinct spatial patterns of higher or lower atrophy than expected. Interpretation: These data support the notion that a measure of deviation from a normative relationship between tau burden and neurodegeneration across brain regions in individuals on the AD continuum captures variability due to multiple underlying factors, and can reveal phenotypes, which if validated, may help identify possible contributors to neurodegeneration in addition to tau, which may ultimately be useful for cohort selection in clinical trials. ANN NEUROL 2021;90:751–762