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Multisite study of the relationships between antemortem [ 11 C]PIB‐PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology
Open accessAbstract
Introduction: We sought to establish the relationships between standard postmortem measures of AD neuropathology and antemortem [ 11 C]PIB–positron emission tomography ([ 11 C]PIB‐PET) analyzed with the Centiloid (CL) method, a standardized scale for Aβ‐PET quantification. Methods: Four centers contributed 179 participants encompassing a broad range of clinical diagnoses, PET data, and autopsy findings. Results: CL values increased with each CERAD neuritic plaque score increment (median −3 CL for no plaques and 92 CL for frequent plaques) and nonlinearly with Thal Aβ phases (increases were detected starting at phase 2) with overlap between scores/phases. PET‐pathology associations were comparable across sites and unchanged when restricting the analyses to the 56 patients who died within 2 years of PET. A threshold of 12.2 CL detected CERAD moderate‐to‐frequent neuritic plaques (area under the curve = 0.910, sensitivity = 89.2%, specificity = 86.4%), whereas 24.4 CL identified intermediate‐to‐high AD neuropathological changes (area under the curve = 0.894, sensitivity = 84.1%, specificity = 87.9%). Discussion: Our study demonstrated the robustness of a multisite Centiloid [ 11 C]PIB‐PET study and established a range of pathology‐based CL thresholds.
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“PET scans were read as positive or negative, as previously described and validated against neuropathology.27”
From Plasma Tau and Neurofilament Light in Frontotemporal Lobar Degeneration and Alzheimer Disease (2021) · cites this paper as [27]
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“The 12-Centiloid threshold is the optimal cut-off validated in neuropathology to detect CERAD moderate-to-frequent, neuritic plaque scores19, early detection of Aβ abnormalities by PET22 and agreement against CSF AD biomarkers18.”
From Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease (2022) · cites this paper as [19]
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“From this work, ≤20 CL is an accepted threshold for amyloid negativity.”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [85]
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“18 F-flutemetamol, 18 F-florbetaben and 18 F-florbetapir tracers display 85%-98% sensitivity and 87%-100% specificity for Aβ plaques when using the postmortem truth standards of the Consortium to Establish a Registry for AD (CERAD) or the National Institute on Aging-Alzheimer's Association 85,[136][137][138] .”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [85]
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Self-citationCho, H., Mundada, N. S., Apostolova, L. G., Carrillo, M. C., Shankar, R. P., Amuiri, A. N., Zeltzer, E., Windon, C., Soleimani‐Meigooni, D. N., Tanner, J. A., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13453 · Cited by 81
Self-citationRabinovici, G. D., Knopman, D. S., Arbizu, J., Benzinger, T. L. S., Donohoe, K. J., Hansson, O., Herscovitch, P., Kuo, P. H., Lingler, J. H., Minoshima, S., et al. (2025) · Journal of Nuclear Medicine · doi:10.2967/jnumed.124.268756 · Cited by 87
Self-citationAmyloid‐β PET in Alzheimer's disease: A systematic review and Bayesian meta‐analysis
Ruan, D., & Sun, L. (2022) · Brain and Behavior · doi:10.1002/brb3.2850 · Cited by 85
Peet, B. T., Spina, S., Mundada, N., & La Joie, R. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01101-x · Cited by 74
Self-citationEarly detection of amyloid load using 18F-florbetaben PET
Bullich, S., Roé-Vellvé, N., Marquié, M., Landau, S. M., Barthel, H., Villemagne, V. L., Sanabria, Á., Tartari, J. P., Sotolongo-Grau, O., Doré, V., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00807-6 · Cited by 71
Self-citationPlasma Phosphorylated Tau 217 to Identify Preclinical Alzheimer Disease
Salvadó, G., Janelidze, S., Bali, D., Dolado, A. O., Therriault, J., Brum, W. S., Binette, A. P., Stomrud, E., Mattsson, N., Palmqvist, S., et al. (2025) · JAMA Neurology · doi:10.1001/jamaneurol.2025.3217 · Cited by 88
Self-citationCollij, L. E., Salvadó, G., Shekari, M., Alves, I. L., Reimand, J., Wink, A. M., Zwan, M. D., Niñerola‐Baizán, A., Perissinotti, A., Scheltens, P., et al. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-020-05174-2 · Cited by 71
ApoE4 and Connectivity-Mediated Spreading of Tau Pathology at Lower Amyloid Levels
Steward, A., Biel, D., Dewenter, A., Roemer, S., Wagner, F., Dehsarvi, A., Rathore, S., Otero Svaldi, D., Higgins, I., Brendel, M., et al. (2023) · JAMA Neurology · doi:10.1001/jamaneurol.2023.4038 · Cited by 67
Frequency and Clinical Outcomes Associated With Tau Positron Emission Tomography Positivity
Moscoso, A., Heeman, F., Raghavan, S., Costoya‐Sánchez, A., van Essen, M., Mainta, I., Camacho, V., Fonseca, O. D. R., Silva‐Rodríguez, J., Perissinotti, A., et al. (2025) · JAMA · doi:10.1001/jama.2025.7817 · Cited by 74
Self-citationPET molecular imaging for pathophysiological visualization in Alzheimer’s disease
Wang, J., Jin, C., Zhou, J., Zhou, R., Tian, M., Lee, H. J., & Zhang, H. (2022) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-022-05999-z · Cited by 71
rPOP: Robust PET-only processing of community acquired heterogeneous amyloid-PET data
Iaccarino, L., Joie, R. L., Koeppe, R. A., Siegel, B. A., Hillner, B. E., Gatsonis, C. A., Whitmer, R. A., Carrillo, M. C., Apgar, C., Camacho, M. R., et al. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118775 · Cited by 64
Self-citationThe Spatial-Temporal Ordering of Amyloid Pathology and Opportunities for PET Imaging
Fantoni, E., Collij, L. E., Alves, I. L., Buckley, C. J., & Farrar, G. (2019) · Journal of Nuclear Medicine · doi:10.2967/jnumed.119.235879 · Cited by 65
Knopman, D. S., Lundt, E. S., Therneau, T. M., Albertson, S. M., Gunter, J. L., Senjem, M. L., Schwarz, C. G., Mielke, M. M., Machulda, M. M., Boeve, B. F., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2020.3921 · Cited by 61
Self-citationAlber, J., Bouwman, F. H., den Haan, J., Rissman, R. A., Groef, L. D., Koronyo‐Hamaoui, M., Lengyel, I., & Thal, D. R. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13529 · Cited by 64
A practical overview of the use of amyloid-PET Centiloid values in clinical trials and research
Iaccarino, L., Burnham, S. C., Tunali, I., Wang, J., Navitsky, M. A., Arora, A., & Pontecorvo, M. J. (2025) · NeuroImage Clinical · doi:10.1016/j.nicl.2025.103765 · Cited by 68
Plasma p217+tau versus NAV4694 amyloid and MK6240 tau PET across the Alzheimer's continuum
Doré, V., Doecke, J. D., Saad, Z. S., Triana‐Baltzer, G., Slemmon, R., Krishnadas, N., Bourgeat, P., Huang, K., Burnham, S. C., Fowler, C. J., et al. (2022) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12307 · Cited by 56
Self-citationGhirelli, A., Tosakulwong, N., Weigand, S. D., Clark, H. M., Ali, F., Botha, H., Duffy, J. R., Utianski, R. L., Buciuc, M., Murray, M. E., et al. (2020) · Annals of Neurology · doi:10.1002/ana.25893 · Cited by 59
Self-citationPlasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer's disease
Devanarayan, V., Doherty, T., Charil, A., Sachdev, P., Ye, Y., Murali, L. K., Llano, D. A., Zhou, J., Reyderman, L., Hampel, H. J., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14073 · Cited by 61
Regional Tau Effects on Prospective Cognitive Change in Cognitively Normal Older Adults
Chen, X., Cassady, K. E., Adams, J. N., Harrison, T. M., Baker, S. L., & Jagust, W. J. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.2111-20.2020 · Cited by 61
Self-citationFink, H. A., Linskens, E. J., Silverman, P. C., McCarten, J. R., Hemmy, L. S., Ouellette, J. M., Greer, N. L., Wilt, T. J., & Butler, M. (2020) · Annals of Internal Medicine · doi:10.7326/m19-3888 · Cited by 57
Murray, M. E., Moloney, C. M., Kouri, N., Syrjanen, J. A., Matchett, B. J., Rothberg, D. M., Tranovich, J. F., Sirmans, T. N. H., Wiste, H. J., Boon, B. D. C., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00578-0 · Cited by 58
Self-citationSon, H. J., Oh, J. S., Oh, M., Kim, S. J., Lee, J., Roh, J. H., & Kim, J. S. (2019) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04595-y · Cited by 52
Salvadó, G., Grothe, M. J., Groot, C., Moscoso, A., Schöll, M., Gispert, J. D., Ossenkoppele, R., & Initiative, A. D. N. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05192-8 · Cited by 57
Therriault, J., Pascoal, T. A., Savard, M., Mathotaarachchi, S. S., Benedet, A. L., Chamoun, M., Tissot, C., Lussier, F. Z., Rahmouni, N., Stevenson, J., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abc8693 · Cited by 58
Stress testing the Centiloid: Precision and variability of PET quantification of amyloid pathology
Shekari, M., García, D. V., Collij, L. E., Altomare, D., Heeman, F., Pemberton, H., Roé-Vellvé, N., Bullich, S., Buckley, C. J., Stephens, A. W., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13883 · Cited by 54
Self-citationLeuzy, A., Rakêt, L. L., Villemagne, V. L., Klein, G., Tonietto, M., Olafson, E., Baker, S. L., Saad, Z. S., Bullich, S., Lopresti, B. J., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13908 · Cited by 53
Self-citationMoscoso, A., Karikari, T. K., Grothe, M. J., Ashton, N. J., Lantero‐Rodriguez, J., Snellman, A., Zetterberg, H., Blennow, K., & Schöll, M. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12570 · Cited by 50
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Self-citationCostoya‐Sánchez, A., Moscoso, A., Silva‐Rodríguez, J., Pontecorvo, M. J., Devous, M. D., Aguiar, P., Schöll, M., Grothe, M. J., Initiative, A. D. N., Weiner, M. W., et al. (2023) · JAMA Neurology · doi:10.1001/jamaneurol.2023.2560 · Cited by 52
Self-citationAdvances in Brain Amyloid Imaging
Krishnadas, N., Villemagne, V. L., Doré, V., & Rowe, C. C. (2021) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2020.12.005 · Cited by 48
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Jovalekic, A., Roé-Vellvé, N., Koglin, N., Lagos‐Quintana, M., Nelson, A. S., Diemling, M., Lilja, J., Gómez-González, J. P., Doré, V., Bourgeat, P., et al. (2023) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-023-06279-0 · Cited by 47
Self-citationAsken, B. M., Tanner, J. A., VandeVrede, L., Mantyh, W. G., Casaletto, K. B., Staffaroni, A. M., La Joie, R., Iaccarino, L., Soleimani-Meigooni, D., Rojas, J. C., et al. (2022) · Neurology · doi:10.1212/wnl.0000000000200678 · Cited by 40
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Self-citationJack, C. R., Wiste, H. J., Algeciras‐Schimnich, A., Weigand, S. D., Figdore, D. J., Lowe, V. J., Vemuri, P., Graff‐Radford, J., Ramanan, V. K., Knopman, D. S., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13651 · Cited by 46
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Self-citationAlzheimer's disease neuropathology and its estimation with fluid and imaging biomarkers
Thal, D. R., Poesen, K., Vandenberghe, R. R., & Meyer, S. D. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00819-y · Cited by 55
Concordance Between Amyloid-PET Quantification and Real-World Visual Reads
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Self-citation
Metadata
- Authors
- La Joie, R., Ayakta, N., Seeley, W. W., Borys, E., Boxer, A. L., DeCarli, C., Doré, V., Grinberg, L. T., Huang, E., Hwang, J., Ikonomovic, M. D., Jack, C., Jagust, W. J., Jin, L., Klunk, W. E., Kofler, J., Lesman‐Segev, O. H., Lockhart, S. N., Lowe, V. J., Masters, C. L., Mathis, C. A., McLean, C. L., Miller, B. L., Mungas, D., O'Neil, J. P., Olichney, J. M., Parisi, J. E., Petersen, R. C., Rosen, H. J., Rowe, C. C., Spina, S., Vemuri, P., Villemagne, V. L., Murray, M. E., & Rabinovici, G. D.
- Affiliations
- Memory & Aging Center Department of Neurology University of California San Francisco CA USA
- University of California, San Francisco (US)
- Loyola University Chicago (US)
- University of California, Davis (US)
- Austin Health (AU)
- Department of Neurology University of Pittsburgh PA USA
- Mayo Clinic (US)
- University of California, Berkeley (US)
- University of Pittsburgh (US)
- Wake Forest University Health Sciences (US)
- The University of Melbourne (AU)
- The Alfred Hospital (AU)
- Helen Wills Neuroscience Institute University of California Berkeley CA USA
- ORCID
- Ayakta, Nagehan
- Seeley, William W.
- Boxer, Adam L.
- DeCarli, Charles
- Doré, Vincent
- Grinberg, Lea T.
- Huang, Eric
- Hwang, Ji‐Hye
- Jack, Clifford
- Jagust, William J.
- Klunk, William E.
- Kofler, Julia
- Lesman‐Segev, Orit H.
- Lockhart, Samuel N.
- Lowe, Val J.
- Masters, Colin L.
- Mathis, Chester A.
- McLean, Catriona L.
- Miller, Bruce L.
- Olichney, John M.
- Petersen, Ronald C.
- Rosen, Howard J.
- Rowe, Christopher C.
- Spina, Salvatore
- Vemuri, Prashanthi
- Villemagne, Victor L.
- Murray, Melissa E.
- Rabinovici, Gil D.
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2018-10-19
- Volume
- 15
- Issue
- 2
- Pages
- 205-216
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC6368897
- OpenAlex
- W2897964327
- Cited by
- 317
- References
- 47
- Citations by year
- 2026: 49 · 2025: 72 · 2024: 51 · 2023: 31 · 2022: 40 · 2021: 42 · 2020: 22 · 2019: 10
- FWCI
- 14.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Biogen
- Genentech
- GE Healthcare
- National Institutes of Health
- National Institute on Aging
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- Alzheimer's disease, 11C-PiB PET
- MeSH terms
- Neuropathology, Aged, Alzheimer Disease, Aniline Compounds, Autopsy, Female, Humans, Male, Retrospective Studies, Thiazoles, Positron-Emission Tomography, Plaque, Amyloid
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