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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]
In the citing paper
“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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PET imagining in Alzheimer’s disease
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Characterizing amyloid and tau PET-based stages across the clinical continuumPreprint
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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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