TY - JOUR
T1 - Staging tau pathology with tau PET in Alzheimer’s disease
T2 - a longitudinal study
AU - for the Alzheimer's Disease Neuroimaging Initiative
AU - Chen, Shi Dong
AU - Lu, Jia Ying
AU - Li, Hong Qi
AU - Yang, Yu Xiang
AU - Jiang, Jie Hui
AU - Cui, Mei
AU - Zuo, Chuan Tao
AU - Tan, Lan
AU - Dong, Qiang
AU - Yu, Jin Tai
AU - Weiner, Michael W.
AU - Aisen, Paul
AU - Petersen, Ronald
AU - Jack, Clifford R.
AU - Jagust, William
AU - Trojanowki, John Q.
AU - Toga, Arthur W.
AU - Beckett, Laurel
AU - Green, Robert C.
AU - Saykin, Andrew J.
AU - Morris, John C.
AU - Perrin, Richard J.
AU - Shaw, Leslie M.
AU - Carrillo, Maria
AU - Potter, William
AU - Barnes, Lisa
AU - Bernard, Marie
AU - González, Hector
AU - Ho, Carole
AU - Hsiao, John K.
AU - Jackson, Jonathan
AU - Masliah, Eliezer
AU - Masterman, Donna
AU - Okonkwo, Ozioma
AU - Ryan, Laurie
AU - Silverberg, Nina
AU - Fleisher, Adam
AU - Sacrey, Diana Truran
AU - Fockler, Juliet
AU - Conti, Cat
AU - Veitch, Dallas
AU - Neuhaus, John
AU - Jin, Chengshi
AU - Nosheny, Rachel
AU - Ashford, Miriam
AU - Flenniken, Derek
AU - Kormos, Adrienne
AU - Rafii, Michael
AU - Raman, Rema
AU - Jimenez, Gustavo
AU - Donohue, Michael
AU - Gessert, Devon
AU - Salazar, Jennifer
AU - Zimmerman, Caileigh
AU - Cabrera, Yuliana
AU - Walter, Sarah
AU - Miller, Garrett
AU - Coker, Godfrey
AU - Clanton, Taylor
AU - Hergesheimer, Lindsey
AU - Smith, Stephanie
AU - Adegoke, Olusegun
AU - Mahboubi, Payam
AU - Moore, Shelley
AU - Pizzola, Jeremy
AU - Shaffer, Elizabeth
AU - Sloan, Brittany
AU - Harvey, Danielle
AU - Forghanian-Arani, Arvin
AU - Borowski, Bret
AU - Ward, Chad
AU - Schwarz, Christopher
AU - Jones, David
AU - Gunter, Jeff
AU - Kantarci, Kejal
AU - Senjem, Matthew
AU - Vemuri, Prashanthi
AU - Reid, Robert
AU - Fox, Nick C.
AU - Malone, Ian
AU - Thompson, Paul
AU - Thomopoulos, Sophia I.
AU - Nir, Talia M.
AU - Jahanshad, Neda
AU - DeCarli, Charles
AU - Knaack, Alexander
AU - Fletcher, Evan
AU - Tosun-Turgut, Duygu
AU - Chen, Stephanie Rossi
AU - Choe, Mark
AU - Crawford, Karen
AU - Yushkevich, Paul A.
AU - Das, Sandhitsu
AU - Koeppe, Robert A.
AU - Reiman, Eric M.
AU - Chen, Kewei
AU - Mathis, Chet
AU - Landau, Susan
AU - Cairns, Nigel J.
AU - Householder, Erin
AU - Franklin, Erin
AU - Bernhardt, Haley
AU - Taylor-Reinwald, Lisa
AU - Shaw, Leslie M.
AU - Trojanowki, John Q.
AU - Korecka, Magdalena
AU - Figurski, Michal
AU - Crawford, Karen
AU - Neu, Scott
AU - Saykin, Andrew J.
AU - Nho, Kwangsik
AU - Risacher, Shannon L.
AU - Apostolova, Liana G.
AU - Shen, Li
AU - Foroud, Tatiana M.
AU - Nudelman, Kelly
AU - Faber, Kelley
AU - Wilmes, Kristi
AU - Thal, Leon
AU - Khachaturian, Zaven
AU - Hsiao, John K.
AU - Silbert, Lisa C.
AU - Lind, Betty
AU - Crissey, Rachel
AU - Kaye, Jeffrey A.
AU - Carter, Raina
AU - Dolen, Sara
AU - Quinn, Joseph
AU - Schneider, Lon S.
AU - Pawluczyk, Sonia
AU - Becerra, Mauricio
AU - Teodoro, Liberty
AU - Dagerman, Karen
AU - Spann, Bryan M.
AU - Brewer, James
AU - Vanderswag, Helen
AU - Fleisher, Adam
AU - Ziolkowski, Jaimie
AU - Heidebrink, Judith L.
AU - Zbizek-Nulph, Lisa
AU - Lord, Joanne L.
AU - Mason, Sara S.
AU - Albers, Colleen S.
AU - Knopman, David
AU - Johnson, Kris
AU - Villanueva-Meyer, Javier
AU - Pavlik, Valory
AU - Pacini, Nathaniel
AU - Lamb, Ashley
AU - Kass, Joseph S.
AU - Doody, Rachelle S.
AU - Shibley, Victoria
AU - Chowdhury, Munir
AU - Rountree, Susan
AU - Dang, Mimi
AU - Stern, Yaakov
AU - Honig, Lawrence S.
AU - Mintz, Akiva
AU - Ances, Beau
AU - Winkfield, David
AU - Carroll, Maria
AU - Stobbs-Cucchi, Georgia
AU - Oliver, Angela
AU - Creech, Mary L.
AU - Mintun, Mark A.
AU - Schneider, Stacy
AU - Geldmacher, David
AU - Love, Marissa Natelson
AU - Griffith, Randall
AU - Clark, David
AU - Brockington, John
AU - Marson, Daniel
AU - Grossman, Hillel
AU - Goldstein, Martin A.
AU - Greenberg, Jonathan
AU - Mitsis, Effie
AU - Shah, Raj C.
AU - Lamar, Melissa
AU - Samuels, Patricia
AU - Duara, Ranjan
AU - Greig-Custo, Maria T.
AU - Rodriguez, Rosemarie
AU - Albert, Marilyn
AU - Onyike, Chiadi
AU - Farrington, Leonie
AU - Rudow, Scott
AU - Brichko, Rottislav
AU - Kielb, Stephanie
AU - Smith, Amanda
AU - Raj, Balebail Ashok
AU - Fargher, Kristin
AU - Sadowski, Martin
AU - Wisniewski, Thomas
AU - Shulman, Melanie
AU - Faustin, Arline
AU - Rao, Julia
AU - Castro, Karen M.
AU - Ulysse, Anaztasia
AU - Chen, Shannon
AU - Mathews, Dana
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - A biological research framework to define Alzheimer’ disease with dichotomized biomarker measurement was proposed by National Institute on Aging–Alzheimer’s Association (NIA–AA). However, it cannot characterize the hierarchy spreading pattern of tau pathology. To reflect in vivo tau progression using biomarker, we constructed a refined topographic 18F-AV-1451 tau PET staging scheme with longitudinal clinical validation. Seven hundred and thirty-four participants with baseline 18F-AV-1451 tau PET (baseline age 73.9 ± 7.7 years, 375 female) were stratified into five stages by a topographic PET staging scheme. Cognitive trajectories and clinical progression were compared across stages with or without further dichotomy of amyloid status, using linear mixed-effect models and Cox proportional hazard models. Significant cognitive decline was first observed in stage 1 when tau levels only increased in transentorhinal regions. Rates of cognitive decline and clinical progression accelerated from stage 2 to stage 3 and stage 4. Higher stages were also associated with greater CSF phosphorylated tau and total tau concentrations from stage 1. Abnormal tau accumulation did not appear with normal β-amyloid in neocortical regions but prompt cognitive decline by interacting with β-amyloid in temporal regions. Highly accumulated tau in temporal regions independently led to cognitive deterioration. Topographic PET staging scheme have potentials in early diagnosis, predicting disease progression, and studying disease mechanism. Characteristic tau spreading pattern in Alzheimer’s disease could be illustrated with biomarker measurement under NIA–AA framework. Clinical–neuroimaging–neuropathological studies in other cohorts are needed to validate these findings.
AB - A biological research framework to define Alzheimer’ disease with dichotomized biomarker measurement was proposed by National Institute on Aging–Alzheimer’s Association (NIA–AA). However, it cannot characterize the hierarchy spreading pattern of tau pathology. To reflect in vivo tau progression using biomarker, we constructed a refined topographic 18F-AV-1451 tau PET staging scheme with longitudinal clinical validation. Seven hundred and thirty-four participants with baseline 18F-AV-1451 tau PET (baseline age 73.9 ± 7.7 years, 375 female) were stratified into five stages by a topographic PET staging scheme. Cognitive trajectories and clinical progression were compared across stages with or without further dichotomy of amyloid status, using linear mixed-effect models and Cox proportional hazard models. Significant cognitive decline was first observed in stage 1 when tau levels only increased in transentorhinal regions. Rates of cognitive decline and clinical progression accelerated from stage 2 to stage 3 and stage 4. Higher stages were also associated with greater CSF phosphorylated tau and total tau concentrations from stage 1. Abnormal tau accumulation did not appear with normal β-amyloid in neocortical regions but prompt cognitive decline by interacting with β-amyloid in temporal regions. Highly accumulated tau in temporal regions independently led to cognitive deterioration. Topographic PET staging scheme have potentials in early diagnosis, predicting disease progression, and studying disease mechanism. Characteristic tau spreading pattern in Alzheimer’s disease could be illustrated with biomarker measurement under NIA–AA framework. Clinical–neuroimaging–neuropathological studies in other cohorts are needed to validate these findings.
UR - http://www.scopus.com/inward/record.url?scp=85116567181&partnerID=8YFLogxK
U2 - 10.1038/s41398-021-01602-5
DO - 10.1038/s41398-021-01602-5
M3 - Article
C2 - 34537810
AN - SCOPUS:85116567181
SN - 2158-3188
VL - 11
JO - Translational psychiatry
JF - Translational psychiatry
IS - 1
M1 - 483
ER -