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01-12-2012 | Original Paper

Correspondence between in vivo ¹¹C-PiB-PET amyloid imaging and postmortem, region-matched assessment of plaques

Authors: Ira Driscoll, Juan C. Troncoso, Gay Rudow, Jitka Sojkova, Olga Pletnikova, Yun Zhou, Michael A. Kraut, Luigi Ferrucci, Chester A. Mathis, William E. Klunk, Richard J. O’Brien, Christos Davatzikos, Dean F. Wong, Susan M. Resnick

Published in: Acta Neuropathologica | Issue 6/2012

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 ¹¹C-Pittsburgh compound-B (PiB)-PET ligand remains the most widely studied to date; however, regional variations in ¹¹C-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 ¹¹C-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 ¹¹C-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 ¹¹C-PiB-PET imaging as a method for evaluation of plaque burden in vivo.

Bacskai BJ, Frosch MP, Freeman SH, Raymond SB, Augustinack JC, Johnson KA, Irizarry MC, Klunk WE, Mathis CA, Dekosky ST, Greenberg SM, Hyman BT, Growdon JH (2007) Molecular imaging with Pittsburgh compound B confirmed at autopsy: a case report. Arch Neurol 64(3):431–434PubMedCrossRef

Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol 82(4):239–259PubMedCrossRef

Burack MA, Hartlein J, Flores HP, Taylor-Reinwald L, Perlmutter JS, Cairns NJ (2010) In vivo amyloid imaging in autopsy-confirmed Parkinson disease with dementia. Neurology 74(1):77–84PubMedCrossRef

Cairns NJ, Ikonomovic MD, Benzinger T, Storandt M, Fagan AM, Shah AR, Reinwald LT, Carter D, Felton A, Holtzman DM, Mintun MA, Klunk WE, Morris JC (2009) Absence of Pittsburgh compound B detection of cerebral amyloid beta in a patient with clinical, cognitive, and cerebrospinal fluid markers of Alzheimer disease: a case report. Arch Neurol 66(12):1557–1562PubMedCrossRef

Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, Pontecorvo MJ, Hefti F, Carpenter AP, Flitter ML, Krautkramer MJ, Kung HF, Coleman RE, Doraiswamy PM, Fleisher AS, Sabbagh MN, Sadowsky CH, Reiman EP, Zehntner SP, Skovronsky DM; AV45-A07 Study Group (2011) Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA 305(3):275–283

Davatzikos C, Genc A, Xu D, Resnick SM (2001) Voxel-based morphometry using the RAVENS maps: methods and validation using simulated longitudinal atrophy. Neuroimage 14:1361–1369PubMedCrossRef

Driscoll I, Resnick SM, Troncoso JC, An Y, O’Brien R, Zonderman AB (2006) Impact of Alzheimer’s pathology on cognitive trajectories in nondemented elderly. Ann Neurol 60:688–695PubMedCrossRef

Driscoll I, Davatzikos C, An Y, Wu X, Shen D, Kraut M, Resnick SM (2009) Longitudinal pattern of regional brain volume change differentiates normal aging from MCI. Neurology 72(22):1906–1913PubMedCrossRef

Drzezga A, Grimmer T, Henriksen G, Stangier I, Perneczky R, Diehl-Schmid J, Mathis CA, Klunk WE, Price J, DeKosky S, Wester HJ, Schwaiger M, Kurz A (2008) Imaging of amyloid plaques and cerebral glucose metabolism in semantic dementia and Alzheimer’s disease. Neuroimage 39(2):619–633PubMedCrossRef

10.

Duyckaerts C, Potier MC, Delatour B (2008) Alzheimer disease models and human neuropathology: similarities and differences. Acta Neuropathol 115(1):5–38PubMedCrossRef

11.

Fodero-Tavoletti MT, Smith DP, McLean CA, Adlard PA, Barnham KJ, Foster LE, Leone L, Perez K, Cortés M, Culvenor JG, Li QX, Laughton KM, Rowe CC, Masters CL, Cappai R, Villemagne VL (2007) In vitro characterization of Pittsburgh compound-B binding to Lewy bodies. J Neurosci 27(39):10365–10371PubMedCrossRef

12.

Forsberg A, Engler H, Almkvist O, Blomquist G, Hagman G, Wall A, Ringheim A, Långström B, Nordberg A (2008) PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging 29(10):1456–1465PubMedCrossRef

13.

Goldszal AF, Davatzikos C, Pham DL, Yan MX, Bryan RN, Resnick SM (1998) An image-processing system for qualitative and quantitative volumetric analysis of brain images. J Comput Assist Tomogr 22:827–837PubMedCrossRef

14.

Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353–356PubMedCrossRef

15.

Ikonomovic MD, Klunk WE, Abrahamson EE, Mathis CA, Price JC, Tsopelas ND, Lopresti BJ, Ziolko S, Bi W, Paljug WR, Debnath ML, Hope CE, Isanski BA, Hamilton RL, DeKosky ST (2008) Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease. Brain 131:1630–1645PubMedCrossRef

16.

Ikonomovic MD, Abrahamson EE, Price JC, Hamilton RL, Mathis CA, Paljug WR, Debnath ML, Cohen AD, Mizukami K, DeKosky ST, Lopez OL, Klunk WE (2012) Early AD pathology in a [C-11]PiB-negative case: a PiB-amyloid imaging, biochemical, and immunohistochemical study. Acta Neuropathol 123(3):433–447PubMedCrossRef

17.

Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ (2010) Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol 9(1):119–128PubMedCrossRef

18.

Kadir A, Almkvist O, Forsberg A, Wall A, Engler H, Långström B, Nordberg A (2012) Dynamic changes in PET amyloid and FDG imaging at different stages of Alzheimer’s disease. Neurobiol Aging 33(1):198.e1–14

19.

Kantarci K, Yang C, Schneider JA, Senjem ML, Reyes DA, Lowe VJ, Barnes LL, Aggarwal NT, Bennett DA, Smith GE, Petersen RC, Jack CR Jr, Boeve BF (2012) Antemortem amyloid imaging and β-amyloid pathology in a case with dementia with Lewy bodies. Neurobiol Aging 33(5):878–885

20.

Kawas C, Gray S, Brookmeyer R, Fozard J, Zonderman A (2000) Age-specific incidence rates of Alzheimer’s disease: the Baltimore Longitudinal Study of Aging. Neurology 54(11):2072–2077PubMedCrossRef

21.

Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, Bergström M, Savitcheva I, Huang GF, Estrada S, Ausén B, Debnath ML, Barletta J, Price JC, Sandell J, Lopresti BJ, Wall A, Koivisto P, Antoni G, Mathis CA, Långström B (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh compound-B. Ann Neurol 55(3):306–319PubMedCrossRef

22.

Koivunen J, Pirttilä T, Kemppainen N, Aalto S, Herukka SK, Jauhianen AM, Hänninen T, Hallikainen M, Någren K, Rinne JO, Soininen H (2008) PET amyloid ligand [¹¹C]PIB uptake and cerebrospinal fluid beta-amyloid in mild cognitive impairment. Dement Geriatr Cogn Disord 26(4):378–383PubMedCrossRef

23.

Lockhart A, Lamb JR, Osredkar T, Sue LI, Joyce JN, Ye L, Libri V, Leppert D, Beach TG (2007) PIB is a non-specific imaging marker of amyloid-beta (Abeta) peptide-related cerebral amyloidosis. Brain 130:2607–2615PubMedCrossRef

24.

McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, Salmon DP, Lowe J, Mirra SS, Byrne EJ, Lennox G, Quinn NP, Edwardson JA, Ince PG, Bergeron C, Burns A, Miller BL, Lovestone S, Collerton D, Jansen EN, Ballard C, de Vos RA, Wilcock GK, Jellinger KA, Perry RH (1996) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 47(5):1113–1124PubMedCrossRef

25.

Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC (2006) [¹¹C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology 67(3):446–452PubMedCrossRef

26.

Mirra SS, Hart MN, Terry RD (1993) Making the diagnosis of Alzheimer’s disease. A primer for practicing pathologists. Arch Pathol Lab Med 117(2):132–144PubMed

27.

Morris JC (1993) The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 43:2412–2414PubMedCrossRef

28.

Ng SY, Villemagne VL, Masters CL, Rowe CC (2007) Evaluating atypical dementia syndromes using positron emission tomography with carbon 11 labeled Pittsburgh compound B. Arch Neurol 64:1140–1144PubMedCrossRef

29.

Okello A, Koivunen J, Edison P, Archer HA, Turkheimer FE, Någren K, Bullock R, Walker Z, Kennedy A, Fox NC, Rossor MN, Rinne JO, Brooks DJ (2009) Conversion of amyloid positive and negative MCI to AD over 3 years: an ¹¹C-PIB PET study. Neurology 73(10):754–760PubMedCrossRef

30.

Price JC, Klunk WE, Lopresti BJ, Lu X, Hoge JA, Ziolko SK, Holt DP, Meltzer CC, DeKosky ST, Mathis CA (2005) Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh compound-B. J Cereb Blood Flow Metab 25(11):1528–1547PubMedCrossRef

31.

Rabinovici GD, Furst AJ, O’Neil JP, Racine CA, Mormino EC, Baker SL, Chetty S, Patel P, Pagliaro TA, Klunk WE, Mathis CA, Rosen HJ, Miller BL, Jagust WJ (2007) ¹¹C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology 68(15):1205–1212PubMedCrossRef

32.

Resnick SM, Goldszal AF, Davatzikos C, Golski S, Kraut MA, Metter EJ, Bryan RN, Zonderman AB (2000) One-year age changes in MRI brain volumes in older adults. Cereb Cortex 10:464–472PubMedCrossRef

33.

Resnick SM, Pham DL, Kraut MA, Zonderman AB, Davatzikos C (2003) Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J Neurosci 23:3295–3301PubMed

34.

Rosen RF, Ciliax BJ, Wingo TS, Gearing M, Dooyema J, Lah JJ, Ghiso JA, LeVine H 3rd, Walker LC (2010) Deficient high-affinity binding of Pittsburgh compound B in a case of Alzheimer’s disease. Acta Neuropathol 119(2):221–233PubMedCrossRef

35.

Rowe CC, Ng S, Ackermann U, Gong SJ, Pike K, Savage G, Cowie TF, Dickinson KL, Maruff P, Darby D, Smith C, Woodward M, Merory J, Tochon-Danguy H, O’Keefe G, Klunk WE, Mathis CA, Price JC, Masters CL, Villemagne VL (2007) Imaging beta-amyloid burden in aging and dementia. Neurology 68:718–1725CrossRef

36.

Shen D, Davatzikos C (2002) HAMMER: hierarchical attribute matching mechanism for elastic registration. IEEE Trans Med Imaging 21:1421–1439PubMedCrossRef

37.

Sojkova J, Driscoll I, Iacono D, Zhou Y, Codispoti KE, Kraut MA, Ferrucci L, Pletnikova O, Mathis CA, Klunk WE, O’Brien RJ, Wong DF, Troncoso JC, Resnick SM (2011) In vivo fibrillar beta-amyloid detected using [¹¹C]PiB positron emission tomography and neuropathologic assessment in older adults. Arch Neurol 68(2):232–240PubMedCrossRef

38.

Villemagne VL, McLean CA, Reardon K, Boyd A, Lewis V, Klug G, Jones G, Baxendale D, Masters CL, Rowe CC, Collins SJ (2009) ¹¹C-PiB PET studies in typical sporadic Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry 80(9):998–1001PubMedCrossRef

39.

Wolk DA, Price JC, Saxton JA, Snitz BE, James JA, Lopez OL, Aizenstein HJ, Cohen AD, Weissfeld LA, Mathis CA, Klunk WE, DeKosky ST (2009) Amyloid imaging in mild cognitive impairment subtypes. Ann Neurol 65(5):557–568PubMedCrossRef

40.

Zhou Y, Endres CJ, Brasić JR, Huang SC, Wong DF (2003) Linear regression with spatial constraint to generate parametric images of ligand–receptor dynamic PET studies with a simplified reference tissue model. Neuroimage 18(4):975–989PubMedCrossRef

41.

Zhou Y, Resnick SM, Ye W, Fan H, Holt DP, Klunk WE, Mathis CA, Dannals R, Wong DF (2007) Using a reference tissue model with spatial constraint to quantify [¹¹C]Pittsburgh compound B PET for early diagnosis of Alzheimer’s disease. Neuroimage 36(2):298–312PubMedCrossRef

Title: Correspondence between in vivo 11C-PiB-PET amyloid imaging and postmortem, region-matched assessment of plaques
Authors: Ira Driscoll
Juan C. Troncoso
Gay Rudow
Jitka Sojkova
Olga Pletnikova
Yun Zhou
Michael A. Kraut
Luigi Ferrucci
Chester A. Mathis
William E. Klunk
Richard J. O’Brien
Christos Davatzikos
Dean F. Wong
Susan M. Resnick
Publication date: 01-12-2012
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 6/2012
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-012-1025-1

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Correspondence between in vivo ¹¹C-PiB-PET amyloid imaging and postmortem, region-matched assessment of plaques

Abstract

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