title: Regional correlations between [11C]PIB PET and post-mortem burden of amyloid-beta pathology in a diverse neuropathological cohort.
abstract: Imaging-pathological correlation studies show thatin vivoamyloid-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 toin vivoPET 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.
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, USA; Lawrence Berkeley National Laboratory, USA; Departments of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Republic of Korea.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Seo
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, USA; Lawrence Berkeley National Laboratory, USA.
authors.forename: Nagehan
authors.initials: N
authors.lastname: Ayakta
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA; Department of Pathology, University of California, San Francisco, USA.
authors.forename: Lea T
authors.initials: LT
authors.lastname: Grinberg
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, USA; Department of Psychiatry, McGill University, Montreal, Canada.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Villeneuve
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA; Dementia Research Centre, University College London, London, United Kingdom.
authors.forename: Manja
authors.initials: M
authors.lastname: Lehmann
authors.affiliation: Center for Scientific Review, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, School of Medicine, University of California, Davis, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Reed
authors.affiliation: Department of Neurology, School of Medicine, University of California, Davis, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Rosen
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Boxer
authors.affiliation: Lawrence Berkeley National Laboratory, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: O'Neil
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Davis, USA.
authors.forename: Lee-Way
authors.initials: LW
authors.lastname: Jin
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, USA; Lawrence Berkeley National Laboratory, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, USA; Lawrence Berkeley National Laboratory, USA.
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D052160:Benzothiazoles; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D003704:Dementia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D013844:Thiazoles
keywords: Alzheimer’s disease; Amyloid; Imaging; Pathology