Multisite study of the relationships between antemortem [11C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology

Renaud La Joie; Nagehan Ayakta; William W Seeley; Ewa Borys; Adam L Boxer; Charles DeCarli; Vincent Doré; Lea T Grinberg; Eric Huang; Ji-Hye Hwang; Milos D Ikonomovic; Clifford Jack Jr; William J Jagust; Lee-Way Jin; William E Klunk; Julia Kofler; Orit H Lesman-Segev; Samuel N Lockhart; Val J Lowe; Colin L Masters; Chester A Mathis; Catriona L McLean; Bruce L Miller; Daniel Mungas; James P O'Neil; John M Olichney; Joseph E Parisi; Ronald C Petersen; Howard J Rosen; Christopher C Rowe; Salvatore Spina; Prashanthi Vemuri; Victor L Villemagne; Melissa E Murray; Gil D Rabinovici

doi:10.1016/j.jalz.2018.09.001

Multisite study of the relationships between antemortem [¹¹C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology

Alzheimers Dement. 2019 Feb;15(2):205-216. doi: 10.1016/j.jalz.2018.09.001. Epub 2018 Oct 19.

Authors

Renaud La Joie¹, Nagehan Ayakta², William W Seeley³, Ewa Borys⁴, Adam L Boxer³, Charles DeCarli⁵, Vincent Doré⁶, Lea T Grinberg³, Eric Huang³, Ji-Hye Hwang³, Milos D Ikonomovic⁷, Clifford Jack Jr⁸, William J Jagust⁹, Lee-Way Jin¹⁰, William E Klunk¹¹, Julia Kofler¹², Orit H Lesman-Segev³, Samuel N Lockhart¹³, Val J Lowe¹⁴, Colin L Masters¹⁵, Chester A Mathis¹⁶, Catriona L McLean¹⁷, Bruce L Miller³, Daniel Mungas⁵, James P O'Neil¹⁸, John M Olichney⁵, Joseph E Parisi¹⁹, Ronald C Petersen²⁰, Howard J Rosen³, Christopher C Rowe⁶, Salvatore Spina³, Prashanthi Vemuri⁸, Victor L Villemagne²¹, Melissa E Murray²², Gil D Rabinovici²

Affiliations

¹ Memory & Aging Center, Department of Neurology, University of California, San Francisco, CA, USA. Electronic address: Renaud.lajoie@ucsf.edu.
² Memory & Aging Center, Department of Neurology, University of California, San Francisco, CA, USA; Helen Wills Neuroscience Institute, University of California Berkeley, CA, USA.
³ Memory & Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
⁴ Department of Pathology, Stritch School of Medicine, Loyola University, Maywood, IL, USA.
⁵ Department of Neurology, University of California, Davis, CA, USA.
⁶ Department of Molecular Imaging & Therapy, Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
⁷ Department of Neurology, University of Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh, PA, USA.
⁸ Department of Radiology, Mayo Clinic, Rochester, MN, USA.
⁹ Helen Wills Neuroscience Institute, University of California Berkeley, CA, USA.
¹⁰ Alzheimer's Disease Center, Department of Pathology, University of California Davis, CA, USA.
¹¹ Department of Neurology, University of Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh, PA, USA; Alzheimer's Disease Research Center, University of Pittsburgh, PA, USA.
¹² Department of Pathology, University of Pittsburgh, Pennsylvania, USA.
¹³ Helen Wills Neuroscience Institute, University of California Berkeley, CA, USA; Department of Internal Medicine, Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
¹⁴ Department of Nuclear Medicine, Mayo Clinic, Rochester, MN, USA.
¹⁵ The Florey Institute, The University of Melbourne, Melbourne, Victoria, Australia.
¹⁶ Department of Radiology, University of Pittsburgh, PA, USA.
¹⁷ Department of Anatomical Pathology, Alfred Hospital, Melbourne, Australia.
¹⁸ Helen Wills Neuroscience Institute, University of California Berkeley, CA, USA; Biomedical Isotope Facility, MBIB Division, Lawrence Berkeley National Laboratory, CA, USA.
¹⁹ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Department of Neurology, Mayo Clinic, Rochester, MN, USA.
²⁰ Department of Neurology, Mayo Clinic, Rochester, MN, USA.
²¹ Department of Molecular Imaging & Therapy, Centre for PET, Austin Health, Heidelberg, Victoria, Australia; The Florey Institute, The University of Melbourne, Melbourne, Victoria, Australia.
²² Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.

Abstract

Introduction: We sought to establish the relationships between standard postmortem measures of AD neuropathology and antemortem [¹¹C]PIB-positron emission tomography ([¹¹C]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 [¹¹C]PIB-PET study and established a range of pathology-based CL thresholds.

Keywords: Alzheimer's disease neuropathologic changes; CERAD; Centiloid; Harmonization; Neuropathology; Pittsburgh compound-B; Positron emission tomography; Thal; Threshold; β-amyloid.

Publication types

Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease* / diagnostic imaging
Alzheimer Disease* / pathology
Aniline Compounds*
Autopsy*
Female
Humans
Male
Neuropathology*
Plaque, Amyloid* / diagnostic imaging
Plaque, Amyloid* / pathology
Positron-Emission Tomography*
Retrospective Studies
Thiazoles*

Substances

2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Aniline Compounds
Thiazoles

Abstract

Publication types

MeSH terms

Substances

Grants and funding