Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease

Maass, Anne; Landau, Susan; Baker, Suzanne L.; Horng, Andy; Lockhart, Samuel N.; La Joie, Renaud; Rabinovici, Gil D.; Jagust, William J.

doi:10.1016/j.neuroimage.2017.05.058

Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease

Journal Article · Sat Jun 03 00:00:00 EDT 2017 · NeuroImage

DOI:https://doi.org/10.1016/j.neuroimage.2017.05.058· OSTI ID:1393249

Maass, Anne ^[1]; Landau, Susan ^[2]; Baker, Suzanne L. ^[3]; Horng, Andy ^[2]; Lockhart, Samuel N. ^[2]; La Joie, Renaud ^[4]; Rabinovici, Gil D. ^[5]; Jagust, William J. ^[5]

Univ. of California, Berkeley, CA (United States); German Center for Neurodegenerative Diseases, Magdeburg (Germany)
Univ. of California, Berkeley, CA (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Univ. of California, San Francisco, CA (United States)
Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, San Francisco, CA (United States)

The recent development of tau-specific positron emission tomography (PET) tracers enables in vivo quantification of regional tau pathology, one of the key lesions in Alzheimer's disease (AD). Tau PET imaging may become a useful biomarker for clinical diagnosis and tracking of disease progression but there is no consensus yet on how tau PET signal is best quantified. The goal of the current paper was to evaluate multiple whole-brain and region-specific approaches to detect clinically relevant tau PET signal. Two independent cohorts of cognitively normal adults and amyloid-positive (Aβ⁺) patients with mild cognitive impairment (MCI) or AD-dementia underwent [¹⁸F]AV-1451 PET. Methods for tau tracer quantification included: (i) in vivo Braak staging, (ii) regional uptake in Braak composite regions, (iii) several whole-brain measures of tracer uptake, (iv) regional uptake in AD-vulnerable voxels, and (v) uptake in a priori defined regions. Receiver operating curves characterized accuracy in distinguishing Aβ^- controls from AD/MCI patients and yielded tau positivity cutoffs. Clinical relevance of tau PET measures was assessed by regressions against cognition and MR imaging measures. Key tracer uptake patterns were identified by a factor analysis and voxel-wise contrasts. Braak staging, global and region-specific tau measures yielded similar diagnostic accuracies, which differed between cohorts. While all tau measures were related to amyloid and global cognition, memory and hippocampal/entorhinal volume/thickness were associated with regional tracer retention in the medial temporal lobe. Key regions of tau accumulation included medial temporal and inferior/middle temporal regions, retrosplenial cortex, and banks of the superior temporal sulcus. Finally, our data indicate that whole-brain tau PET measures might be adequate biomarkers to detect AD-related tau pathology. However, regional measures covering AD-vulnerable regions may increase sensitivity to early tau PET signal, atrophy and memory decline.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States); Univ. of California, San Francisco, CA (United States)

Sponsoring Organization:: National Inst. of Health (NIH) (United States); USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1393249

Journal Information:: NeuroImage, Journal Name: NeuroImage Vol. 157; ISSN 1053-8119

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

References (44)

Neuropathologic Features of Amnestic Mild Cognitive Impairment Petersen, Ronald C.; Parisi, Joseph E.; Dickson, Dennis W. Archives of Neurology, Vol. 63, Issue 5 https://doi.org/10.1001/archneur.63.5.665	journal	May 2006
Association of Lifetime Cognitive Engagement and Low β-Amyloid Deposition Marks, Shawn M. Archives of Neurology, Vol. 69, Issue 5 https://doi.org/10.1001/archneurol.2011.2748	journal	May 2012
Evaluation of Tau Imaging in Staging Alzheimer Disease and Revealing Interactions Between β-Amyloid and Tauopathy Wang, Liang; Benzinger, Tammie L.; Su, Yi JAMA Neurology, Vol. 73, Issue 9 https://doi.org/10.1001/jamaneurol.2016.2078	journal	September 2016
Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue: Validation of PET Tracer Marquié, Marta; Normandin, Marc D.; Vanderburg, Charles R. Annals of Neurology, Vol. 78, Issue 5 https://doi.org/10.1002/ana.24517	journal	September 2015
Tau positron emission tomographic imaging in aging and early Alzheimer disease: Tau PET in Aging and Early AD Johnson, Keith A.; Schultz, Aaron; Betensky, Rebecca A. Annals of Neurology, Vol. 79, Issue 1 https://doi.org/10.1002/ana.24546	journal	December 2015
In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum: Tau and Amyloid in AD Cho, Hanna; Choi, Jae Yong; Hwang, Mi Song Annals of Neurology, Vol. 80, Issue 2 https://doi.org/10.1002/ana.24711	journal	July 2016
Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease: Origin and Spread of Atrophy in AD Variants Ossenkoppele, Rik; Cohn-Sheehy, Brendan I.; La Joie, Renaud Human Brain Mapping, Vol. 36, Issue 11 https://doi.org/10.1002/hbm.22927	journal	August 2015
Discrimination between Alzheimer Dementia and Controls by Automated Analysis of Multicenter FDG PET Herholz, K.; Salmon, E.; Perani, D. NeuroImage, Vol. 17, Issue 1 https://doi.org/10.1006/nimg.2002.1208	journal	September 2002
Neuropathological stageing of Alzheimer-related changes Braak, H.; Braak, E. Acta Neuropathologica, Vol. 82, Issue 4 https://doi.org/10.1007/BF00308809	journal	September 1991
Tau imaging in neurodegenerative diseases Dani, M.; Brooks, D. J.; Edison, P. European Journal of Nuclear Medicine and Molecular Imaging, Vol. 43, Issue 6 https://doi.org/10.1007/s00259-015-3231-2	journal	November 2015
Primary age-related tauopathy (PART): a common pathology associated with human aging Crary, John F.; Trojanowski, John Q.; Schneider, Julie A. Acta Neuropathologica, Vol. 128, Issue 6 https://doi.org/10.1007/s00401-014-1349-0	journal	October 2014
“Mini-mental state” Folstein, Marshal F.; Folstein, Susan E.; McHugh, Paul R. Journal of Psychiatric Research, Vol. 12, Issue 3 https://doi.org/10.1016/0022-3956(75)90026-6	journal	November 1975
Basic principles of ROC analysis Metz, Charles E. Seminars in Nuclear Medicine, Vol. 8, Issue 4 https://doi.org/10.1016/S0001-2998(78)80014-2	journal	October 1978
Frequency of Stages of Alzheimer-Related Lesions in Different Age Categories Braak, H.; Braak, E. Neurobiology of Aging, Vol. 18, Issue 4 https://doi.org/10.1016/S0197-4580(97)00056-0	journal	July 1997
Tau imaging: early progress and future directions Villemagne, Victor L.; Fodero-Tavoletti, Michelle T.; Masters, Colin L. The Lancet Neurology, Vol. 14, Issue 1 https://doi.org/10.1016/S1474-4422(14)70252-2	journal	January 2015
Clinical core of the Alzheimer's disease neuroimaging initiative: Progress and plans Aisen, Paul S.; Petersen, Ronald C.; Donohue, Michael C. Alzheimer's & Dementia, Vol. 6, Issue 3 https://doi.org/10.1016/j.jalz.2010.03.006	journal	May 2010
The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease McKhann, Guy M.; Knopman, David S.; Chertkow, Howard Alzheimer's & Dementia, Vol. 7, Issue 3 https://doi.org/10.1016/j.jalz.2011.03.005	journal	May 2011
The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease Albert, Marilyn S.; DeKosky, Steven T.; Dickson, Dennis Alzheimer's & Dementia, Vol. 7, Issue 3 https://doi.org/10.1016/j.jalz.2011.03.008	journal	April 2011
Ic‐02‐03: Existing Thresholds for pib Positivity are too high Villeneuve, Sylvia; Madison, Cindee; Ayakta, Nagehan Alzheimer's & Dementia, Vol. 10, Issue 4S_Part_1 https://doi.org/10.1016/j.jalz.2014.04.026	journal	July 2014
Phase 3 solanezumab trials: Secondary outcomes in mild Alzheimer's disease patients Siemers, Eric R.; Sundell, Karen L.; Carlson, Christopher Alzheimer's & Dementia, Vol. 12, Issue 2 https://doi.org/10.1016/j.jalz.2015.06.1893	journal	July 2015
ICI‐02‐01: Alzheimer's Disease Imaging Biomarkers and Aging Jack, Clifford R. Alzheimer's & Dementia, Vol. 12, Issue 7S_Part_1 https://doi.org/10.1016/j.jalz.2016.06.077	journal	July 2016
Reducing between scanner differences in multi-center PET studies Joshi, Aniket; Koeppe, Robert A.; Fessler, Jeffrey A. NeuroImage, Vol. 46, Issue 1 https://doi.org/10.1016/j.neuroimage.2009.01.057	journal	May 2009
Characterizing Alzheimer's disease using a hypometabolic convergence index Chen, Kewei; Ayutyanont, Napatkamon; Langbaum, Jessica B. S. NeuroImage, Vol. 56, Issue 1 https://doi.org/10.1016/j.neuroimage.2011.01.049	journal	May 2011
Not quite PIB-positive, not quite PIB-negative: Slight PIB elevations in elderly normal control subjects are biologically relevant Mormino, Elizabeth C.; Brandel, Michael G.; Madison, Cindee M. NeuroImage, Vol. 59, Issue 2 https://doi.org/10.1016/j.neuroimage.2011.07.098	journal	January 2012
PET Imaging of Tau Deposition in the Aging Human Brain Schöll, Michael; Lockhart, Samuel N.; Schonhaut, Daniel R. Neuron, Vol. 89, Issue 5 https://doi.org/10.1016/j.neuron.2016.01.028	journal	March 2016
Kinetic Modeling of Amyloid Binding in Humans using PET Imaging and Pittsburgh Compound-B Price, Julie C.; Klunk, William E.; Lopresti, Brian J. Journal of Cerebral Blood Flow & Metabolism, Vol. 25, Issue 11 https://doi.org/10.1038/sj.jcbfm.9600146	journal	May 2005
Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer's disease Desikan, R. S.; Cabral, H. J.; Hess, C. P. Brain, Vol. 132, Issue 8 https://doi.org/10.1093/brain/awp123	journal	May 2009
Existing Pittsburgh Compound-B positron emission tomography thresholds are too high: statistical and pathological evaluation Villeneuve, Sylvia; Rabinovici, Gil D.; Cohn-Sheehy, Brendan I. Brain, Vol. 138, Issue 7 https://doi.org/10.1093/brain/awv112	journal	May 2015
Regional profiles of the candidate tau PET ligand ¹⁸ F-AV-1451 recapitulate key features of Braak histopathological stages Schwarz, Adam J.; Yu, Peng; Miller, Bradley B. Brain, Vol. 139, Issue 5 https://doi.org/10.1093/brain/aww023	journal	March 2016
Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease Ossenkoppele, Rik; Schonhaut, Daniel R.; Schöll, Michael Brain, Vol. 139, Issue 5 https://doi.org/10.1093/brain/aww027	journal	March 2016
The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals Dickerson, Bradford C.; Bakkour, Akram; Salat, David H. Cerebral Cortex, Vol. 19, Issue 3 https://doi.org/10.1093/cercor/bhn113	journal	July 2008
Neuropathology of Cognitively Normal Elderly Knopman, D. S.; Parisi, J. E.; Salviati, A. Journal of Neuropathology & Experimental Neurology, Vol. 62, Issue 11 https://doi.org/10.1093/jnen/62.11.1087	journal	November 2003
Distribution Volume Ratios without Blood Sampling from Graphical Analysis of PET Data Logan, Jean; Fowler, Joanna S.; Volkow, Nora D. Journal of Cerebral Blood Flow & Metabolism, Vol. 16, Issue 5 https://doi.org/10.1097/00004647-199609000-00008	journal	September 1996
Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease Brier, Matthew R.; Gordon, Brian; Friedrichsen, Karl Science Translational Medicine, Vol. 8, Issue 338 https://doi.org/10.1126/scitranslmed.aaf2362	journal	May 2016
Tau PET imaging: present and future directions Saint-Aubert, Laure; Lemoine, Laetitia; Chiotis, Konstantinos Molecular Neurodegeneration, Vol. 12, Issue 1 https://doi.org/10.1186/s13024-017-0162-3	journal	February 2017
Regional tau deposition measured by [18F]THK5317 positron emission tomography is associated to cognition via glucose metabolism in Alzheimer’s disease Saint-Aubert, Laure; Almkvist, Ove; Chiotis, Konstantinos Alzheimer's Research & Therapy, Vol. 8, Issue 1 https://doi.org/10.1186/s13195-016-0204-z	journal	September 2016
Tau PET in Alzheimer disease and mild cognitive impairment Cho, Hanna; Choi, Jae Yong; Hwang, Mi Song Neurology, Vol. 87, Issue 4 https://doi.org/10.1212/WNL.0000000000002892	journal	June 2016
A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers Jack, Clifford R.; Bennett, David A.; Blennow, Kaj Neurology, Vol. 87, Issue 5 https://doi.org/10.1212/WNL.0000000000002923	journal	July 2016
Alzheimer's Disease Neuroimaging Initiative (ADNI): Clinical characterization Petersen, R. C.; Aisen, P. S.; Beckett, L. A. Neurology, Vol. 74, Issue 3 https://doi.org/10.1212/WNL.0b013e3181cb3e25	journal	December 2009
Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease Jack, C. R.; Petersen, R. C.; Xu, Y. C. Neurology, Vol. 49, Issue 3 https://doi.org/10.1212/WNL.49.3.786	journal	September 1997
The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer's disease Delacourte, A.; David, J. P.; Sergeant, N. Neurology, Vol. 52, Issue 6 https://doi.org/10.1212/WNL.52.6.1158	journal	April 1999
Nonparametric Bayesian sparse factor models with application to gene expression modeling Knowles, David; Ghahramani, Zoubin The Annals of Applied Statistics, Vol. 5, Issue 2B https://doi.org/10.1214/10-AOAS435	journal	June 2011
In Vivo Tau, Amyloid, and Gray Matter Profiles in the Aging Brain Sepulcre, J.; Schultz, A. P.; Sabuncu, M. Journal of Neuroscience, Vol. 36, Issue 28 https://doi.org/10.1523/JNEUROSCI.0639-16.2016	journal	July 2016
Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F-18]-T807 Chien, David T.; Bahri, Shadfar; Szardenings, A. Katrin Journal of Alzheimer's Disease, Vol. 34, Issue 2 https://doi.org/10.3233/JAD-122059	journal	June 2013

Cited By (22)

Discovery and preclinical characterization of [18F]PI-2620, a next-generation tau PET tracer for the assessment of tau pathology in Alzheimer’s disease and other tauopathies Kroth, Heiko; Oden, Felix; Molette, Jerome European Journal of Nuclear Medicine and Molecular Imaging, Vol. 46, Issue 10 https://doi.org/10.1007/s00259-019-04397-2	journal	July 2019
Topographic staging of tau positron emission tomography images Schwarz, Adam J.; Shcherbinin, Sergey; Slieker, Lawrence J. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Vol. 10, Issue 1 https://doi.org/10.1016/j.dadm.2018.01.006	journal	January 2018
European Ultrahigh‐Field Imaging Network for Neurodegenerative Diseases (EUFIND) Düzel, Emrah; Acosta‐Cabronero, Julio; Berron, David Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Vol. 11, Issue 1 https://doi.org/10.1016/j.dadm.2019.04.010	journal	July 2019
NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease Jack, Clifford R.; Bennett, David A.; Blennow, Kaj Alzheimer's & Dementia, Vol. 14, Issue 4 https://doi.org/10.1016/j.jalz.2018.02.018	journal	April 2018
Distinct tau PET patterns in atrophy‐defined subtypes of Alzheimer's disease Ossenkoppele, Rik; Lyoo, Chul Hyoung; Sudre, Carole H. Alzheimer's & Dementia, Vol. 16, Issue 2 https://doi.org/10.1016/j.jalz.2019.08.201	journal	January 2020
Prediction of fast decline in amyloid positive mild cognitive impairment patients using multimodal biomarkers Jang, Hyemin; Park, Jongyun; Woo, Sookyoung NeuroImage: Clinical, Vol. 24 https://doi.org/10.1016/j.nicl.2019.101941	journal	January 2019
Modelling prognostic trajectories of cognitive decline due to Alzheimer's disease Giorgio, Joseph; Landau, Susan M.; Jagust, William J. NeuroImage: Clinical, Vol. 26 https://doi.org/10.1016/j.nicl.2020.102199	journal	January 2020
Alzheimer's disease drug development pipeline: 2018 Cummings, Jeffrey; Lee, Garam; Ritter, Aaron Alzheimer's & Dementia: Translational Research & Clinical Interventions, Vol. 4, Issue 1 https://doi.org/10.1016/j.trci.2018.03.009	journal	January 2018
Tau PET imaging in neurodegenerative tauopathies—still a challenge Leuzy, Antoine; Chiotis, Konstantinos; Lemoine, Laetitia Molecular Psychiatry, Vol. 24, Issue 8 https://doi.org/10.1038/s41380-018-0342-8	journal	January 2019
Tau deposition is associated with functional isolation of the hippocampus in aging Harrison, Theresa M.; Maass, Anne; Adams, Jenna N. Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-12921-z	journal	October 2019
Functional brain architecture is associated with the rate of tau accumulation in Alzheimer’s disease Franzmeier, Nicolai; Neitzel, Julia; Rubinski, Anna Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-019-14159-1	journal	January 2020
Longitudinal tau PET in ageing and Alzheimer’s disease Jack, Clifford R.; Wiste, Heather J.; Schwarz, Christopher G. Brain, Vol. 141, Issue 5 https://doi.org/10.1093/brain/awy059	journal	March 2018
Neuroanatomical spread of amyloid β and tau in Alzheimer’s disease: implications for primary prevention Insel, Philip S.; Mormino, Elizabeth C.; Aisen, Paul S. Brain Communications, Vol. 2, Issue 1 https://doi.org/10.1093/braincomms/fcaa007	journal	January 2020
Is tau in the absence of amyloid on the Alzheimer’s continuum?: A study of discordant PET positivity Weigand, Alexandra J.; Bangen, Katherine J.; Thomas, Kelsey R. Brain Communications, Vol. 2, Issue 1 https://doi.org/10.1093/braincomms/fcz046	journal	December 2019
Neuroimaging Biomarkers for Alzheimer’s Disease Márquez, Freddie; Yassa, Michael A. Molecular Neurodegeneration, Vol. 14, Issue 1 https://doi.org/10.1186/s13024-019-0325-5	journal	June 2019
Data-driven prognostic features of cognitive trajectories in patients with amnestic mild cognitive impairments Kim, Yeo Jin; Cho, Seong-Kyoung; Kim, Hee Jin Alzheimer's Research & Therapy, Vol. 11, Issue 1 https://doi.org/10.1186/s13195-018-0462-z	journal	January 2019
A walk through tau therapeutic strategies. Jadhav, Santosh; Avila, Jesus; Schöll, Michael Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.39320	text	January 2019
Dissociation of Tau Deposits and Brain Atrophy in Early Alzheimer’s Disease: A Combined Positron Emission Tomography/Magnetic Resonance Imaging Study Shigemoto, Yoko; Sone, Daichi; Imabayashi, Etsuko Frontiers in Aging Neuroscience, Vol. 10 https://doi.org/10.3389/fnagi.2018.00223	journal	July 2018
Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients Zhao, Qian; Liu, Min; Ha, Lingxia Frontiers in Neurology, Vol. 10 https://doi.org/10.3389/fneur.2019.00486	journal	May 2019
Disrupted Functional Connectivity of Cornu Ammonis Subregions in Amnestic Mild Cognitive Impairment: A Longitudinal Resting-State fMRI Study Li, Hui; Jia, Xiuqin; Qi, Zhigang Frontiers in Human Neuroscience, Vol. 12 https://doi.org/10.3389/fnhum.2018.00413	journal	October 2018
Audiovisual Lexical Retrieval Deficits Following Left Hemisphere Stroke Hanna-Pladdy, Brenda; Choi, Hyun; Herman, Brian Brain Sciences, Vol. 8, Issue 12 https://doi.org/10.3390/brainsci8120206	journal	November 2018
Cortical tau deposition follows patterns of entorhinal functional connectivity in aging Adams, Jenna N.; Maass, Anne; Harrison, Theresa M. eLife, Vol. 8 https://doi.org/10.7554/elife.49132	journal	September 2019

Similar Records

PET Imaging of Tau Deposition in the Aging Human Brain

Journal Article · Tue Mar 01 19:00:00 EST 2016 · Neuron · OSTI ID:1379129

Early detection of amyloid load using 18F-florbetaben PET

Journal Article · Fri Mar 26 20:00:00 EDT 2021 · Alzheimer's Research & Therapy · OSTI ID:1816049

The impact of demographic, clinical, genetic, and imaging variables on tau PET status

Journal Article · Wed Nov 18 19:00:00 EST 2020 · European Journal of Nuclear Medicine and Molecular Imaging · OSTI ID:1816071

Related Subjects

60 APPLIED LIFE SCIENCES
AV-1451
Alzheimer's disease
biomarker
positron emission tomography
tau
β-amyloid

Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease

Citation Formats

References (44)

Cited By (22)

Similar Records

Related Subjects