Regional correlations between [ 11 C]PIB PET and post-mortem burden of amyloid-beta pathology in a diverse neuropathological cohort

Seo, Sang Won; Ayakta, Nagehan; Grinberg, Lea T.; Villeneuve, Sylvia; Lehmann, Manja; Reed, Bruce; DeCarli, Charles; Miller, Bruce L.; Rosen, Howard J.; Boxer, Adam L.; O’Neil, James P.; Jin, Lee-Way; Seeley, William W.; Jagust, William J.; Rabinovici, Gil D.

doi:10.1016/j.nicl.2016.11.008

Regional correlations between [ 11 C]PIB PET and post-mortem burden of amyloid-beta pathology in a diverse neuropathological cohort

Journal Article · Sat Dec 31 23:00:00 EST 2016 · NeuroImage: Clinical

DOI:https://doi.org/10.1016/j.nicl.2016.11.008· OSTI ID:1623706

Seo, Sang Won ^[1]; Ayakta, Nagehan ^[2]; Grinberg, Lea T. ^[3]; Villeneuve, Sylvia ^[4]; Lehmann, Manja ^[5]; Reed, Bruce ^[6]; DeCarli, Charles ^[7]; Miller, Bruce L. ^[8]; Rosen, Howard J. ^[8]; Boxer, Adam L. ^[8]; O’Neil, James P. ^[9]; Jin, Lee-Way ^[10]; Seeley, William W. ^[8]; Jagust, William J. ^[11]; Rabinovici, Gil D. ^[2]

University of California, San Francisco (United States). Memory and Aging Center, Department of Neurology; University of California, Berkeley (United States). Helen Wills Neuroscience Institute; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sungkyunkwan University School of Medicine (Republic of Korea). Departments of Neurology, Samsung Medical Center; DOE/OSTI
University of California, San Francisco (United States). Memory and Aging Center, Department of Neurology; University of California, Berkeley (United States). Helen Wills Neuroscience Institute; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
University of California, San Francisco (United States). Memory and Aging Center, Department of Neurology; University of California, San Francisco (United States). Department of Pathology
University of California, Berkeley (United States). Helen Wills Neuroscience Institute; McGill University, Montreal (Canada). Department of Psychiatry
University of California, San Francisco (United States). Memory and Aging Center, Department of Neurology; University College London, London (United Kingdom). Dementia Research Centre
National Institutes of Health, Bethesda, MD (United States). Center for Scientific Review; University of California, Davis (United States). Department of Neurology, School of Medicine
University of California, Davis (United States). Department of Neurology, School of Medicine
University of California, San Francisco (United States). Memory and Aging Center, Department of Neurology
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
University of California, Davis (United States). Department of Pathology and Laboratory Medicine
University of California, San Francisco (United States). Memory and Aging Center, Department of Neurology; University of California, Berkeley (United States). Helen Wills Neuroscience Institute; University of California, San Francisco (United States). Department of Pathology

Imaging-pathological correlation studies show that in vivo amyloid-β (Aβ) positron emission tomography (PET) strongly predicts the presence of significant Aβ pathology at autopsy. We sought to determine whether regional PiB-PET uptake would improve sensitivity for amyloid detection in comparison with global measures (experiment 1), and to estimate the relative contributions of different Aβ aggregates to in vivo PET signal (experiment 2). In experiment 1, 54 subjects with [11C] PiB-PET during life and postmortem neuropathologic examination (85.2% with dementia, interval from PET to autopsy 3.1 ± 1.9 years) were included. We assessed Thal amyloid phase (N = 36) and CERAD score (N = 54) versus both global and regional PiB SUVRs. In experiment 2 (N = 42), PiB SUVR and post-mortem amyloid β burden was analyzed in five customized regions of interest matching regions sampled at autopsy. We assessed the relative contribution of neuritic plaques (NPs), diffuse plaques (DPs) and cerebral amyloid angiopathy (CAA) to regional PIB SUVR using multi-linear regression. In experiment 1, there were no differences in Area Under the Curve for amyloid phase ≥ A2 and CERAD score ≥ C2 between global and highest regional PiB SUVR (p = 0.186 and 0.230). In experiment 2, when NPs, DPs, and/or CAA were included in the same model, moderate to severe NPs were independently correlated with PiB SUVR in all regions except for the inferior temporal and calcarine ROI (β = 0.414–0.804, p < 0.05), whereas DPs were independently correlated with PiB SUVR in the angular gyrus ROI (β = 0.446, p = 0.010). CAA was also associated with PiB SUVR in the inferior temporal and calcarine ROI (β = 0.222–0.355, p < 0.05). In conclusion, global PiB-PET SUVR performed as well as regional values for amyloid detection in our cohort. The substrate-specific binding of PiB might differ among the brain specific regions.

View Accepted Manuscript (DOE)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1623706

Journal Information:: NeuroImage: Clinical, Journal Name: NeuroImage: Clinical Journal Issue: C Vol. 13; ISSN 2213-1582

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

References (36)

Molecular Imaging With Pittsburgh Compound B Confirmed at Autopsy: A Case Report Bacskai, Brian J.; Frosch, Matthew P.; Freeman, Stefanie H. Archives of Neurology, Vol. 64, Issue 3 https://doi.org/10.1001/archneur.64.3.431	journal	March 2007
In Vivo Fibrillar β-Amyloid Detected Using [11C]PiB Positron Emission Tomography and Neuropathologic Assessment in Older Adults Sojkova, Jitka; Driscoll, Ira; Iacono, Diego Archives of Neurology, Vol. 68, Issue 2 https://doi.org/10.1001/archneurol.2010.357	journal	February 2011
Phase 3 Trial of Flutemetamol Labeled With Radioactive Fluorine 18 Imaging and Neuritic Plaque Density Curtis, Craig; Gamez, Jose E.; Singh, Upinder JAMA Neurology, Vol. 72, Issue 3 https://doi.org/10.1001/jamaneurol.2014.4144	journal	March 2015
Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain Tzourio-Mazoyer, N.; Landeau, B.; Papathanassiou, D. NeuroImage, Vol. 15, Issue 1 https://doi.org/10.1006/nimg.2001.0978	journal	January 2002
Modified Bielschowsky stain and immunohistochemical studies on striatal plaques in Alzheimer's disease Suenaga, T.; Hirano, A.; Llena, J. F. Acta Neuropathologica, Vol. 80, Issue 3 https://doi.org/10.1007/BF00294646	journal	July 1990
In vivo amyloid imaging with PET in frontotemporal dementia Engler, Henry; Santillo, Alexander Frizell; Wang, Shu Xia European Journal of Nuclear Medicine and Molecular Imaging, Vol. 35, Issue 1 https://doi.org/10.1007/s00259-007-0523-1	journal	September 2007
Longitudinal imaging of Alzheimer pathology using [11C]PIB, [18F]FDDNP and [18F]FDG PET Ossenkoppele, Rik; Tolboom, Nelleke; Foster-Dingley, Jessica C. European Journal of Nuclear Medicine and Molecular Imaging, Vol. 39, Issue 6 https://doi.org/10.1007/s00259-012-2102-3	journal	March 2012
Five-year follow-up of 11C-PIB uptake in Alzheimer’s disease and MCI Kemppainen, N. M.; Scheinin, N. M.; Koivunen, J. European Journal of Nuclear Medicine and Molecular Imaging, Vol. 41, Issue 2 https://doi.org/10.1007/s00259-013-2562-0	journal	September 2013
Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update Mackenzie, Ian R. A.; Neumann, Manuela; Bigio, Eileen H. Acta Neuropathologica, Vol. 119, Issue 1 https://doi.org/10.1007/s00401-009-0612-2	journal	November 2009
National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach Montine, Thomas J.; Phelps, Creighton H.; Beach, Thomas G. Acta Neuropathologica, Vol. 123, Issue 1 https://doi.org/10.1007/s00401-011-0910-3	journal	November 2011
Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study Clark, Christopher M.; Pontecorvo, Michael J.; Beach, Thomas G. The Lancet Neurology, Vol. 11, Issue 8 https://doi.org/10.1016/S1474-4422(12)70142-4	journal	August 2012
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
National Institute on Aging–Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease Hyman, Bradley T.; Phelps, Creighton H.; Beach, Thomas G. Alzheimer's & Dementia, Vol. 8, Issue 1 https://doi.org/10.1016/j.jalz.2011.10.007	journal	January 2012
Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: Phase 3 study Sabri, Osama; Sabbagh, Marwan N.; Seibyl, John Alzheimer's & Dementia, Vol. 11, Issue 8 https://doi.org/10.1016/j.jalz.2015.02.004	journal	March 2015
Ante mortem amyloid imaging and β-amyloid pathology in a case with dementia with Lewy bodies Kantarci, Kejal; Yang, Chunhui; Schneider, Julie A. Neurobiology of Aging, Vol. 33, Issue 5 https://doi.org/10.1016/j.neurobiolaging.2010.08.007	journal	May 2012
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
Measurement of Radiotracer Concentration in Brain Gray Matter Using Positron Emission Tomography: MRI-Based Correction for Partial Volume Effects Müller-Gärtner, Hans W.; Links, Jonathan M.; Prince, Jerry L. Journal of Cerebral Blood Flow & Metabolism, Vol. 12, Issue 4 https://doi.org/10.1038/jcbfm.1992.81	journal	July 1992
PIB is a non-specific imaging marker of amyloid-beta (A ) peptide-related cerebral amyloidosis Lockhart, A.; Lamb, J. R.; Osredkar, T. Brain, Vol. 130, Issue 10 https://doi.org/10.1093/brain/awm191	journal	October 2007
Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease Ikonomovic, Milos D.; Klunk, William E.; Abrahamson, Eric E. Brain, Vol. 131, Issue 6 https://doi.org/10.1093/brain/awn016	journal	March 2008
Increased metabolic vulnerability in early-onset Alzheimer’s disease is not related to amyloid burden Rabinovici, Gil D.; Furst, Ansgar J.; Alkalay, Adi Brain, Vol. 133, Issue 2 https://doi.org/10.1093/brain/awp326	journal	January 2010
Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia Rascovsky, Katya; Hodges, John R.; Knopman, David Brain, Vol. 134, Issue 9 https://doi.org/10.1093/brain/awr179	journal	August 2011
Clinicopathologic and ¹¹ C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer’s disease spectrum Murray, Melissa E.; Lowe, Val J.; Graff-Radford, Neill R. Brain, Vol. 138, Issue 5 https://doi.org/10.1093/brain/awv050	journal	March 2015
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
Vascular Pathology in Alzheimer Disease: Correlation of Cerebral Amyloid Angiopathy and Arteriosclerosis/Lipohyalinosis with Cognitive Decline Thal, Dietmar Rudolf; Ghebremedhin, Estifanos; Orantes, Mario Journal of Neuropathology & Experimental Neurology, Vol. 62, Issue 12 https://doi.org/10.1093/jnen/62.12.1287	journal	December 2003
Neuropathologic Heterogeneity Does Not Impair Florbetapir-Positron Emission Tomography Postmortem Correlates Dugger, Brittany N.; Clark, Christopher M.; Serrano, Geidy Journal of Neuropathology & Experimental Neurology, Vol. 73, Issue 1 https://doi.org/10.1097/NEN.0000000000000028	journal	January 2014
Mild cognitive impairment as a diagnostic entity Petersen, R. C. Journal of Internal Medicine, Vol. 256, Issue 3 https://doi.org/10.1111/j.1365-2796.2004.01388.x	journal	September 2004
[11C]PIB in a nondemented population: Potential antecedent marker of Alzheimer disease Mintun, M. A.; LaRossa, G. N.; Sheline, Y. I. Neurology, Vol. 67, Issue 3 https://doi.org/10.1212/01.wnl.0000228230.26044.a4	journal	August 2006
Imaging -amyloid burden in aging and dementia Rowe, C. C.; Ng, S.; Ackermann, U. Neurology, Vol. 68, Issue 20 https://doi.org/10.1212/01.wnl.0000261919.22630.ea	journal	May 2007
11C-PIB binding is increased in patients with cerebral amyloid angiopathy-related hemorrhage Ly, J. V.; Donnan, G. A.; Villemagne, V. L. Neurology, Vol. 74, Issue 6 https://doi.org/10.1212/WNL.0b013e3181cef7e3	journal	February 2010
Classification of primary progressive aphasia and its variants Gorno-Tempini, M. L.; Hillis, A. E.; Weintraub, S. Neurology, Vol. 76, Issue 11 https://doi.org/10.1212/WNL.0b013e31821103e6	journal	February 2011
Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD Rabinovici, G. D.; Rosen, H. J.; Alkalay, A. Neurology, Vol. 77, Issue 23 https://doi.org/10.1212/WNL.0b013e31823b9c5e	journal	November 2011
Criteria for the diagnosis of corticobasal degeneration Armstrong, M. J.; Litvan, I.; Lang, A. E. Neurology, Vol. 80, Issue 5 https://doi.org/10.1212/WNL.0b013e31827f0fd1	journal	January 2013
The Consortium to Establish a Registry for Alzheimer's Disease (CERAD): Part II. Standardization of the neuropathologic assessment of Alzheimer's disease Mirra, S. S.; Heyman, A.; McKeel, D. Neurology, Vol. 41, Issue 4 https://doi.org/10.1212/WNL.41.4.479	journal	April 1991
The Binding of 2-(4′-Methylaminophenyl)Benzothiazole to Postmortem Brain Homogenates Is Dominated by the Amyloid Component Klunk, William E.; Wang, Yanming; Huang, Guo-feng The Journal of Neuroscience, Vol. 23, Issue 6 https://doi.org/10.1523/JNEUROSCI.23-06-02086.2003	journal	March 2003
Comparing the Areas under Two or More Correlated Receiver Operating Characteristic Curves: A Nonparametric Approach DeLong, Elizabeth R.; DeLong, David M.; Clarke-Pearson, Daniel L. Biometrics, Vol. 44, Issue 3 https://doi.org/10.2307/2531595	journal	September 1988

Cited By (10)

Classification and Visualization of Alzheimer’s Disease using Volumetric Convolutional Neural Network and Transfer Learning Oh, Kanghan; Chung, Young-Chul; Kim, Ko Woon Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-54548-6	journal	December 2019
The emerging role of PET imaging in dementia Iaccarino, Leonardo; Sala, Arianna; Caminiti, Silvia Paola F1000Research, Vol. 6 https://doi.org/10.12688/f1000research.11603.1	journal	January 2017
Classification of Alzheimer's Disease, Mild Cognitive Impairment, and Cognitively Unimpaired Individuals Using Multi-feature Kernel Discriminant Dictionary Learning Li, Qing; Wu, Xia; Xu, Lele Frontiers in Computational Neuroscience, Vol. 11 https://doi.org/10.3389/fncom.2017.00117	journal	January 2018
Subcortical amyloid load is associated with shape and volume in cognitively normal individuals Rahayel, Shady; Bocti, Christian; Sévigny Dupont, Pénélope Human Brain Mapping https://doi.org/10.1002/hbm.24680	journal	May 2019
Amyloid involvement in subcortical regions predicts cognitive decline Cho, Soo Hyun; Shin, Jeong-Hyeon; Jang, Hyemin European Journal of Nuclear Medicine and Molecular Imaging, Vol. 45, Issue 13 https://doi.org/10.1007/s00259-018-4081-5	journal	July 2018
Clinical significance of amyloid β positivity in patients with probable cerebral amyloid angiopathy markers Jang, Hyemin; Jang, Young Kyoung; Kim, Hee Jin European Journal of Nuclear Medicine and Molecular Imaging, Vol. 46, Issue 6 https://doi.org/10.1007/s00259-019-04314-7	journal	April 2019
2018 Alzheimer's disease facts and figures Association, Alzheimer's Alzheimer's & Dementia, Vol. 14, Issue 3, p. 367-429 https://doi.org/10.1016/j.jalz.2018.02.001	journal	January 2018
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
Multisite study of the relationships between antemortem [ ¹¹ C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology La Joie, Renaud; Ayakta, Nagehan; Seeley, William W. Alzheimer's & Dementia, Vol. 15, Issue 2 https://doi.org/10.1016/j.jalz.2018.09.001	journal	October 2018
Multimodal imaging Gd-nanoparticles functionalized with Pittsburgh compound B or a nanobody for amyloid plaques targeting Pansieri, Jonathan; Plissonneau, Marie; Stransky-Heilkron, Nathalie Nanomedicine, Vol. 12, Issue 14 https://doi.org/10.2217/nnm-2017-0079	journal	July 2017

Similar Records

Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease

Journal Article · Wed Mar 12 00:00:00 EDT 2008 · Brain · OSTI ID:1625298

Early detection of amyloid load using 18F-florbetaben PET

Journal Article · Sat Mar 27 00:00:00 EDT 2021 · Alzheimer's Research & Therapy · OSTI ID:1816049

Related Subjects

Neurosciences & Neurology

Regional correlations between [ 11 C]PIB PET and post-mortem burden of amyloid-beta pathology in a diverse neuropathological cohort

Citation Formats

References (36)

Cited By (10)

Similar Records

Related Subjects