title: Correspondence between in vivo (11)C-PiB-PET amyloid imaging and postmortem, region-matched assessment of plaques.
abstract: The definitive Alzheimer's disease (AD) diagnosis requires postmortem confirmation of neuropathological hallmarks-amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). The advent of radiotracers for amyloid imaging presents an opportunity to investigate amyloid deposition in vivo. The (11)C-Pittsburgh compound-B (PiB)-PET ligand remains the most widely studied to date; however, regional variations in (11)C-PiB binding and the extent of agreement with neuropathological assessment have not been thoroughly investigated. Sojkova and colleagues [35] reported variable agreement between CERAD-based neuropathologic diagnosis of AD lesions and mean cortical PiB, suggesting the need for a more direct quantification of regional Aβ in relation to in vivo imaging. In the present study, we extend these findings by examining the correspondence among regional (11)C-PiB load, region-matched quantitative immunohistological assessments of Aβ and NFTs, and brain atrophy (MRI) in six older Baltimore Longitudinal Study of Aging participants who came to autopsy (imaging-autopsy interval range 0.2-2.4 years). The total number of Aβ plaques (6E10) and NFTs (PHF1) in paraffin sections from hippocampus, orbito-frontal cortex, anterior and posterior cingulate gyrus, precuneus and cerebellum was quantified using a technique guided by unbiased stereological principles. We report a general agreement between the regional measures of amyloid obtained via stereological assessment and imaging, with significant relationships evident for the anterior (r = 0.83; p = 0.04) and posterior (r = 0.94; p = 0.005) cingulate gyri, and the precuneus (r = 0.94; p = 0.005). No associations were observed between (11)C-PiB load and NFT count for any of the regions examined (p > 0.2 in all regions), or between regional Aβ or NFT counts and corresponding brain volumes. The strong associations of PiB retention with region-matched, quantitative analyses of Aβ in postmortem tissue offer support for the validity of (11)C-PiB-PET imaging as a method for evaluation of plaque burden in vivo.
authors.affiliation: National Institute on Aging, Baltimore, MD, USA. driscoli@uwm.edu
authors.forename: Ira
authors.initials: I
authors.lastname: Driscoll
authors.forename: Juan C
authors.initials: JC
authors.lastname: Troncoso
authors.forename: Gay
authors.initials: G
authors.lastname: Rudow
authors.forename: Jitka
authors.initials: J
authors.lastname: Sojkova
authors.forename: Olga
authors.initials: O
authors.lastname: Pletnikova
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kraut
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Brien
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001344:Autopsy / Q000379:methods; D052160:Benzothiazoles / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D059906:Neuroimaging / Q000379:methods; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D049268:Positron-Emission Tomography; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D013844:Thiazoles