AUTHOR=Zhao Qian , Liu Min , Ha Lingxia , Zhou Yun , Alzheimer's Disease Neuroimaging Initiative , Weiner Michael W. , Aisen Paul , Weiner Michael , Aisen Paul , Petersen Ronald , Jack Clifford R. , Jagust William , Trojanowki John Q. , Toga Arthur W. , Beckett Laurel , Green Robert C. , Saykin Andrew J. , Morris John , Shaw Leslie M. , Khachaturian Zaven , Sorensen Greg , Carrillo Maria , Kuller Lew , Raichle Marc , Paul Steven , Davies Peter , Fillit Howard , Hefti Franz , Holtzman David , Mesulam M. Marcel , Potter William , Snyder Peter , Schwartz Adam , Green Robert C. , Montine Tom , Petersen Ronald , Aisen Paul , Thomas Ronald G. , Donohue Michael , Walter Sarah , Gessert Devon , Sather Tamie , Jiminez Gus , Balasubramanian Archana B. , Mason Jennifer , Sim Iris , Beckett Laurel , Harvey Danielle , Donohue Michael , Jack Clifford R. , Bernstein Matthew , Fox Nick , Thompson Paul , Schuff Norbert , DeCArli Charles , Borowski Bret , Gunter Jeff , Senjem Matt , Vemuri Prashanthi , Jones David , Kantarci Kejal , Ward Chad , Jagust William , Koeppe Robert A. , Foster Norm , Reiman Eric M. , Chen Kewei , Mathis Chet , Landau Susan , Morris John C. , Cairns Nigel J. , Franklin Erin , Taylor-Reinwald Lisa , Shaw Leslie M. , Trojanowki John Q. , Lee Virginia , Korecka Magdalena , Figurski Michal , Toga Arthur W. , Crawford Karen , Neu Scott , Saykin Andrew J. , Foroud Tatiana M. , Potkin Steven , Shen Li , Faber Kelley , Kim Sungeun , Nho Kwangsik , Weiner Michael W. , Thal Lean , Khachaturian Zaven , Thal Leon , Buckholtz Neil , Weiner Michael W. , Snyder Peter J. , Potter William , Paul Steven , Albert Marilyn , Frank Richard , Khachaturian Zaven , Hsiao John , Kaye Jeffrey , Quinn Joseph , Silbert Lisa , Lind Betty , Carter Raina , Dolen Sara , Schneider Lon S. , Pawluczyk Sonia , Becerra Mauricio , Teodoro Liberty , Spann Bryan M. , Brewer James , Vanderswag Helen , Fleisher Adam , Heidebrink Judith L. , Lord Joanne L. , Petersen Ronald , Mason Sara S. , Albers Colleen S. , Knopman David , Johnson Kris , Doody Rachelle S. , Villanueva-Meyer Javier , Pavlik Valory , Shibley Victoria , Chowdhury Munir , Rountree Susan , Dang Mimi , Stern Yaakov , Honig Lawrence S. , Bell Karen L. , Ances Beau , Morris John C. , Carroll Maria , Creech Mary L. , Franklin Erin , Mintun Mark A. , Schneider Stacy , Oliver Angela , Marson Daniel , Geldmacher David , Natelson Love Marissa , Griffith Randall , Clark David , Brockington John , Roberson Erik , Grossman Hillel , Mitsis Effie , Shah Raj C. , deToledo-Morrell Leyla , Duara Ranjan , Greig-Custo Maria T. , Barker Warren , Albert Marilyn , Onyike Chiadi , D'Agostino Daniel , Kielb Stephanie , Sadowski Martin , Sheikh Mohammed O. , Anaztasia Ulysse , Mrunalini Gaikwad , Doraiswamy P. Murali , Petrella Jeffrey R. , Borges-Neto Salvador , Wong Terence Z. , Coleman Edward , Arnold Steven E. , Karlawish Jason H. , Wolk David A. , Clark Christopher M. , Smith Charles D. , Jicha Greg , Hardy Peter , Sinha Partha , Oates Elizabeth , Conrad Gary , Lopez Oscar L. , Oakley MaryAnn , Simpson Donna M. , Porsteinsson Anton P. , Goldstein Bonnie S. , Martin Kim , Makino Kelly M. , Ismail M. Saleem , Brand Connie , Potkin Steven G. , Preda Adrian , Nguyen Dana , Womack Kyle , Mathews Dana , Quiceno Mary , Levey Allan I. , Lah James J. , Cellar Janet S. , Burns Jeffrey M. , Swerdlow Russell H. , Brooks William M. , Apostolova Liana , Tingus Kathleen , Woo Ellen , Silverman Daniel H.S. , Lu Po H. , Bartzokis George , Graff-Radford Neill R , Parfitt Francine , Poki-Walker Kim , Farlow Martin R. , Hake Ann Marie , Matthews Brandy R. , Brosch Jared R. , Herring Scott , van Dyck Christopher H. , Carson Richard E. , MacAvoy Martha G. , Varma Pradeep , Chertkow Howard , Bergman Howard , Hosein Chris , Black Sandra , Stefanovic Bojana , Caldwell Curtis , Hsiung Ging-Yuek Robin , Mudge Benita , Sossi Vesna , Feldman Howard , Assaly Michele , Finger Elizabeth , Pasternack Stephen , Rachisky Irina , Trost Dick , Kertesz Andrew , Bernick Charles , Munic Donna , Mesulam Marek-Marsel , Rogalski Emily , Lipowski Kristine , Weintraub Sandra , Bonakdarpour Borna , Kerwin Diana , Wu Chuang-Kuo , Johnson Nancy , Sadowsky Carl , Villena Teresa , Turner Raymond Scott , Johnson Kathleen , Reynolds Brigid , Sperling Reisa A. , Johnson Keith A. , Marshall Gad , Yesavage Jerome , Taylor Joy L. , Lane Barton , Rosen Allyson , Tinklenberg Jared , Sabbagh Marwan N. , Belden Christine M. , Jacobson Sandra A. , Sirrel Sherye A. , Kowall Neil , Killiany Ronald , Budson Andrew E. , Norbash Alexander , Johnson Patricia Lynn , Obisesan Thomas O. , Wolday Saba , Allard Joanne , Lerner Alan , Ogrocki Paula , Tatsuoka Curtis , Fatica Parianne , Fletcher Evan , Maillard Pauline , Olichney John , DeCarli Charles , Carmichael Owen , Kittur Smita , Borrie Michael , Lee T-Y , Bartha Rob , Johnson Sterling , Asthana Sanjay , Carlsson Cynthia M. , Potkin Steven G. , Preda Adrian , Nguyen Dana , Tariot Pierre , Burke Anna , Milliken Ann Marie , Trncic Nadira , Fleisher Adam , Reeder Stephanie , Bates Vernice , Capote Horacio , Rainka Michelle , Scharre Douglas W. , Kataki Maria , Kelley Brendan , Zimmerman Earl A. , Celmins Dzintra , Brown Alice D. , Pearlson Godfrey D. , Blank Karen , Anderson Karen , Flashman Laura A. , Seltzer Marc , Hynes Mary L. , Santulli Robert B. , Sink Kaycee M. , Leslie Gordineer , Williamson Jeff D. , Garg Pradeep , Watkins Franklin , Ott Brian R. , Tremont Geoffrey , Daiello Lori A. , Salloway Stephen , Malloy Paul , Correia Stephen , Rosen Howard J. , Miller Bruce L. , Perry David , Mintzer Jacobo , Spicer Kenneth , Bachman David , Finger Elizabeth , Pasternak Stephen , Rachinsky Irina , Rogers John , Kertesz Andrew , Drost Dick , Pomara Nunzio , Hernando Raymundo , Sarrael Antero , Schultz Susan K. , Smith Karen Ekstam , Koleva Hristina , Nam Ki Won , Shim Hyungsub , Relkin Norman , Chiang Gloria , Lin Michael , Ravdin Lisa , Smith Amanda , Raj Balebail Ashok , Fargher Kristin , Weiner Michael W. , Aisen Paul , Weiner Michael , Aisen Paul , Petersen Ronald , Green Robert C. , Harvey Danielle , Jack Clifford R. , Jagust William , Morris John C. , Saykin Andrew J. , Shaw Leslie M. , Toga Arthur W. , Trojanowki John Q. , Neylan Thomas , Grafman Jordan , Green Robert C. , Montine Tom , Weiner Michael , Petersen Ronald , Aisen Paul , Thomas Ronald G. , Donohue Michael , Devon Gessert , Sather Tamie , Melissa Davis , Morrison Rosemary , Jiminez Gus , Neylan Thomas , Jacqueline Hayes , Shannon Finley , Harvey Danielle , Donohue Michael , Jack Clifford R. , Bernstein Matthew , Borowski Bret , Gunter Jeff , Senjem Matt , Kejal Kantarci , Chad Ward , Jagust William , Koeppe Robert A. , Foster Norm , Reiman Eric M. , Chen Kewei , Landau Susan , Morris John C. , Cairns Nigel J. , Householder Erin , Shaw Leslie M. , Trojanowki John Q. , Lee Virginia , Korecka Magdalena , Figurski Michal , Toga Arthur W. , Karen Crawford , Scott Neu , Saykin Andrew J. , Foroud Tatiana M. , Potkin Steven , Shen Li , Faber Kelley , Kim Sungeun , Nho Kwangsik , Weiner Michael W. , Karl Friedl , Schneider Lon S. , Pawluczyk Sonia , Mauricio Becerra , Brewer James , Vanderswag Helen , Stern Yaakov , Honig Lawrence S. , Bell Karen L. , Fleischman Debra , Arfanakis Konstantinos , Shah Raj C. , Duara Ranjan , Varon Daniel , Greig Maria T , Doraiswamy P. Murali , Petrella Jeffrey R. , James Olga , Porsteinsson Anton P. , Goldstein Bonnie , Martin Kimberly S. , Potkin Steven G. , Preda Adrian , Nguyen Dana , Mintzer Jacobo , Massoglia Dino , Brawman-Mintzer Olga , Sadowsky Carl , Martinez Walter , Villena Teresa , Jagust William , Landau Susan , Rosen Howard , Perry David , Turner Raymond Scott , Behan Kelly , Reynolds Brigid , Sperling Reisa A. , Johnson Keith A. , Marshall Gad , Sabbagh Marwan N. , Jacobson Sandra A. , Sirrel Sherye A. , Obisesan Thomas O. , Wolday Saba , Allard Joanne , Johnson Sterling C. , Fruehling J. Jay , Harding Sandra , Peskind Elaine R. , Petrie Eric C. , Li Gail , Yesavage Jerome A. , Taylor Joy L. , Furst Ansgar J. , Chao Steven , Relkin Norman , Chiang Gloria , Ravdin Lisa , Ravdin Lisa , Mackin Scott , Aisen Paul , Raman Rema , Mackin Scott , Weiner Michael , Aisen Paul , Raman Rema , Jack Clifford R. , Landau Susan , Saykin Andrew J. , Toga Arthur W. , DeCarli Charles , Koeppe Robert A. , Green Robert C. , Drake Erin , Weiner Michael , Aisen Paul , Raman Rema , Donohue Mike , Jimenez Gustavo , Gessert Devon , Harless Kelly , Salazar Jennifer , Cabrera Yuliana , Walter Sarah , Hergesheimer Lindsey , Shaffer Elizabeth , Mackin Scott , Nelson Craig , Bickford David , Butters Meryl , Zmuda Michelle , Jack Clifford R. , Bernstein Matthew , Borowski Bret , Gunter Jeff , Senjem Matt , Kantarci Kejal , Ward Chad , Reyes Denise , Koeppe Robert A. , Landau Susan , Toga Arthur W. , Crawford Karen , Neu Scott , Saykin Andrew J. , Foroud Tatiana M. , Faber Kelley M. , Nho Kwangsik , Nudelman Kelly N. , Mackin Scott , Rosen Howard , Nelson Craig , Bickford David , Au Yiu Ho , Scherer Kelly , Catalinotto Daniel , Stark Samuel , Ong Elise , Fernandez Dariella , Butters Meryl , Zmuda Michelle , Lopez Oscar L. , Oakley MaryAnn , Simpson Donna M.
TITLE=Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients
JOURNAL=Frontiers in Neurology
VOLUME=10
YEAR=2019
URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.00486
DOI=10.3389/fneur.2019.00486
ISSN=1664-2295
ABSTRACT=Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.
Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.
Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.
Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification.