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Acta Neuropathologica Communications
Published in: Acta Neuropathologica Communications 1/2016

Open Access 01-12-2016 | Research

Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injection

Authors: Milos D. Ikonomovic, Chris J. Buckley, Kerstin Heurling, Paul Sherwin, Paul A. Jones, Michelle Zanette, Chester A. Mathis, William E. Klunk, Aruna Chakrabarty, James Ironside, Azzam Ismail, Colin Smith, Dietmar R. Thal, Thomas G. Beach, Gill Farrar, Adrian P. L. Smith

Published in: Acta Neuropathologica Communications | Issue 1/2016

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Abstract

In vivo imaging of fibrillar β-amyloid deposits may assist clinical diagnosis of Alzheimer’s disease (AD), aid treatment selection for patients, assist clinical trials of therapeutic drugs through subject selection, and be used as an outcome measure. A recent phase III trial of [18F]flutemetamol positron emission tomography (PET) imaging in 106 end-of-life subjects demonstrated the ability to identify fibrillar β-amyloid by comparing in vivo PET to post-mortem histopathology. Post-mortem analyses demonstrated a broad and continuous spectrum of β-amyloid pathology in AD and other dementing and non-dementing disease groups. The GE067-026 trial demonstrated 91% sensitivity and 90% specificity of [18F]flutemetamol PET by majority read for the presence of moderate or frequent plaques. The probability of an abnormal [18F]flutemetamol scan increased with neocortical plaque density and AD diagnosis. All dementia cases with non-AD neurodegenerative diseases and those without histopathological features of β-amyloid deposits were [18F]flutemetamol negative. Majority PET assessments accurately reflected the amyloid plaque burden in 90% of cases. However, ten cases demonstrated a mismatch between PET image interpretations and post-mortem findings. Although tracer retention was best associated with amyloid in neuritic plaques, amyloid in diffuse plaques and cerebral amyloid angiopathy best explain three [18F]flutemetamol positive cases with mismatched (sparse) neuritic plaque burden. Advanced cortical atrophy was associated with the seven false negative [18F]flutemetamol images. The interpretation of images from pathologically equivocal cases was associated with low reader confidence and inter-reader agreement. Our results support that amyloid in neuritic plaque burden is the primary form of β-amyloid pathology detectable with [18F]flutemetamol PET imaging. ClinicalTrials.gov NCT01165554. Registered June 21, 2010; NCT02090855. Registered March 11, 2014.
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Literature
1.
Alafuzoff I, Pikkarainen M, Arzberger T, Thal DR, Al-Sarraj S, Bell J, Bodi I, Budka H, Capetillo-Zarate E, Ferrer I, Gelpi E, Gentleman S, Giaccone G, Kavantzas N, King A, Korkolopoulou P, Kovacs GG, Meyronet D, Monoranu C, Parchi P, Patsouris E, Roggendorf W, Stadelmann C, Streichenberger N, Tagliavini F, Kretzschmar H (2008) Inter-laboratory comparison of neuropathological assessments of beta-amyloid protein: a study of the BrainNet Europe consortium. Acta Neuropathol 115:533–546CrossRefPubMed
2.
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 64:431–434CrossRefPubMed
3.
Baron JC, Farid K, Dolan E, Turc G, Marrapu ST, O'Brien E, Aigbirhio FI, Fryer TD, Menon DK, Warburton EA, Hong YT (2014) Diagnostic utility of amyloid PET in cerebral amyloid angiopathy-related symptomatic intracerebral hemorrhage. J Cereb Blood Flow Metab 34:753–758CrossRefPubMedPubMedCentral
4.
Beach TG, Monsell SE, Phillips LE, Kukull W (2012) Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010. J Neuropathol Exp Neurol 71:266–273CrossRefPubMedPubMedCentral
5.
Beach TG, Thal DR, Zanette M, Smith A, Buckley C (2016) Detection of striatal amyloid plaques with [18 F] flutemetamol: validation with postmortem histopathology. J Alzheimers Dis 52:863–873CrossRefPubMed
6.
7.
Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259CrossRefPubMed
8.
Braak H, Braak E (1997) Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging 18:351–357CrossRefPubMed
9.
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 74:77–84CrossRefPubMedPubMedCentral
10.
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 66:1557–1562CrossRefPubMedPubMedCentral
11.
Clark CM, Pontecorvo MJ, Beach TG, Bedell BJ, Coleman RE, Doraiswamy PM, Fleisher AS, Reiman EM, Sabbagh MN, Sadowsky CH, Schneider JA, Arora A, Carpenter AP, Flitter ML, Joshi AD, Krautkramer MJ, Lu M, Mintun MA, Skovronsky DM (2012) Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: a prospective cohort study. Lancet Neurol 11:669–678CrossRefPubMed
12.
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 (2011) Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA 305:275–283CrossRefPubMed
13.
Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I, Arnold SE, Attems J, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Gearing M, Grinberg LT, Hof PR, Hyman BT, Jellinger K, Jicha GA, Kovacs GG, Knopman DS, Kofler J, Kukull WA, Mackenzie IR, Masliah E, McKee A, Montine TJ, Murray ME, Neltner JH, Santa-Maria I, Seeley WW, Serrano-Pozo A, Shelanski ML, Stein T, Takao M, Thal DR, Toledo JB, Troncoso JC, Vonsattel JP, White CL, Wisniewski T, Woltjer RL, Yamada M, Nelson PT (2014) Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol (Berl) 128:755–766CrossRef
14.
Curtis C, Gamez JE, Singh U, Sadowsky CH, Villena T, Sabbagh MN, Beach TG, Duara R, Fleisher AS, Frey KA, Walker Z, Hunjan A, Holmes C, Escovar YM, Vera CX, Agronin ME, Ross J, Bozoki A, Akinola M, Shi J, Vandenberghe R, Ikonomovic MD, Sherwin PF, Grachev ID, Farrar G, Smith AP, Buckley CJ, McLain R, Salloway S (2015) Phase 3 trial of flutemetamol labeled with radioactive fluorine 18 Imaging and neuritic plaque density. JAMA Neurol 72(3):287–294CrossRefPubMed
15.
Dickson DW, Wertkin A, Mattiace LA, Fier E, Kress Y, Davies P, Yen SH (1990) Ubiquitin immunoelectron microscopy of dystrophic neurites in cerebellar senile plaques of Alzheimer’s disease. Acta Neuropathol 79:486–493CrossRefPubMed
16.
Dugger BN, Serrano GE, Sue LI, Walker DG, Adler CH, Shill HA, Sabbagh MN, Caviness JN, Hidalgo J, Saxon-Labelle M, Chiarolanza G, Mariner M, Henry-Watson J, Beach TG (2012) Presence of striatal amyloid plaques in parkinson’s disease dementia predicts concomitant Alzheimer’s disease: usefulness for amyloid imaging. J Parkinsons Dis 2:57–65PubMedPubMedCentral
17.
18.
Fleiss JL (1971) Measuring nominal scale agreement among many raters. Psychol Bull 76:378–382CrossRef
19.
Fodero-Tavoletti MT, Smith DP, McLean CA, Adlard PA, Barnham KJ, Foster LE, Leone L, Perez K, Cortes 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 27:10365–10371CrossRefPubMed
20.
Gearing M, Levey AI, Mirra SS (1997) Diffuse plaques in the striatum in Alzheimer disease (AD): relationship to the striatal mosaic and selected neuropeptide markers. J Neuropathol Exp Neurol 56:1363–1370CrossRefPubMed
21.
Geddes JW, Tekirian TL, Soultanian NS, Ashford JW, Davis DG, Markesbery WR (1997) Comparison of neuropathologic criteria for the diagnosis of Alzheimer's disease. Neurobiol Aging 18:S99–S105CrossRefPubMed
22.
Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Dürr A, Fowler CJ, Kaufmann H, Klockgether T, Lees A, Poewe W, Quinn N, Revesz T, Robertson D, Sandroni P, Seppi K, Vidailhet M (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71(9):670–676CrossRefPubMedPubMedCentral
23.
Hauw JJ, Daniel SE, Dickson D, Horoupian DS, Jellinger K, Lantos PL, McKee A, Tabaton M, Litvan I (1994) Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski Syndrome (progressive Supranuclear Palsy). Neurology 44(11):2015–2019CrossRefPubMed
24.
Herholz K, Ebmeier K (2011) Clinical amyloid imaging in Alzheimer's disease. Lancet Neurol 10:667–670CrossRefPubMed
25.
Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Thies B, Trojanowski JQ, Vinters HV, Montine TJ (2012) National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement 8:1–13CrossRefPubMedPubMedCentral
26.
Hyman BT, Trojanowski JQ (1997) Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol 56:1095–1097CrossRefPubMed
27.
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 123:433–447CrossRefPubMedPubMedCentral
28.
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 131:1630–1645CrossRefPubMedPubMedCentral
29.
Jellinger KA, Attems J (2007) Neurofibrillary Tangle-Predominant Dementia: Comparison with Classical Alzheimer Disease. Acta Neuropathol 113(2):107–117CrossRefPubMed
30.
Johnson KA, Gregas M, Becker JA, Kinnecom C, Salat DH, Moran EK, Smith EE, Rosand J, Rentz DM, Klunk WE, Mathis CA, Price JC, DeKosky ST, Fischman AJ, Greenberg SM (2007) Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Ann Neurol 62:229–234CrossRefPubMed
31.
Johnson KA, Sperling RA, Gidicsin CM, Carmasin JS, Maye JE, Coleman RE, Reiman EM, Sabbagh MN, Sadowsky CH, Fleisher AS, Murali DP, Carpenter AP, Clark CM, Joshi AD, Lu M, Grundman M, Mintun MA, Pontecorvo MJ, Skovronsky DM (2013) Florbetapir (F18-AV-45) PET to assess amyloid burden in Alzheimer's disease dementia, mild cognitive impairment, and normal aging. Alzheimers Dement 9:S72–S83CrossRefPubMedPubMedCentral
32.
Kadir A, Marutle A, Gonzalez D, Scholl M, Almkvist O, Mousavi M, Mustafiz T, Darreh-Shori T, Nennesmo I, Nordberg A (2011) Positron emission tomography imaging and clinical progression in relation to molecular pathology in the first Pittsburgh Compound B positron emission tomography patient with Alzheimer's disease. Brain 134:301–317CrossRefPubMed
33.
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 beta-amyloid pathology in a case with dementia with Lewy bodies. Neurobiol Aging 33:878–885CrossRefPubMed
34.
Klunk WE, Price JC, Mathis CA, Tsopelas ND, Lopresti BJ, Ziolko SK, Bi W, Hoge JA, Cohen AD, Ikonomovic MD, Saxton JA, Snitz BE, Pollen DA, Moonis M, Lippa CF, Swearer JM, Johnson KA, Rentz DM, Fischman AJ, Aizenstein HJ, DeKosky ST (2007) Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees. J Neurosci 27:6174–6184CrossRefPubMedPubMedCentral
35.
Landau SM, Breault C, Joshi AD, Pontecorvo M, Mathis CA, Jagust WJ, Mintun MA (2013) Amyloid-beta imaging with Pittsburgh compound B and florbetapir: comparing radiotracers and quantification methods. J Nucl Med 54:70–77CrossRefPubMed
36.
Leinonen V, Alafuzoff I, Aalto S, Suotunen T, Savolainen S, Nagren K, Tapiola T, Pirttila T, Rinne J, Jaaskelainen JE, Soininen H, Rinne JO (2008) Assessment of beta-amyloid in a frontal cortical brain biopsy specimen and by positron emission tomography with carbon 11-labeled Pittsburgh Compound B. Arch Neurol 65:1304–1309CrossRefPubMed
37.
Leinonen V, Rinne JO, Virtanen KA, Eskola O, Rummukainen J, Huttunen J, von Und Zu FM, Nerg O, Koivisto AM, Rinne J, Jaaskelainen JE, Buckley C, Smith A, Jones PA, Sherwin P, Farrar G, McLain R, Kailajarvi M, Heurling K, Grachev ID (2013) Positron emission tomography with [18 F] flutemetamol and [11C]PiB for in vivo detection of cerebral cortical amyloid in normal pressure hydrocephalus patients. Eur J Neurol 20:1043–1052CrossRefPubMed
38.
Leinonen V, Rinne JO, Wong DF, Wolk DA, Trojanowski JQ, Sherwin PF, Smith A, Heurling K, Su M, Grachev ID (2014) Diagnostic effectiveness of quantitative [18 F] flutemetamol PET imaging for detection of fibrillar amyloid beta using cortical biopsy histopathology as the standard of truth in subjects with idiopathic normal pressure hydrocephalus. Acta Neuropathol Commun 2:46CrossRefPubMedPubMedCentral
39.
Litchfield S, Nagy Z (2001) New temperature modification makes the Bielschowsky silver stain reproducible. Acta Neuropathol 101:17–21PubMed
40.
Litvan I, Hauw JJ, Bartko JJ, Lantos PL, Daniel SE, Horoupian DS, McKee A, Dickson D, Bancher C, Tabaton M, Jellinger K, Anderson DW (1996) Validity and reliability of the preliminary NINDS neuropathologic criteria for progressive supranuclear palsy and related disorders. J Neuropathol Exp Neurol 55(1):97–105CrossRefPubMed
41.
Lockhart A, Ye L, Judd DB, Merritt AT, Lowe PN, Morgenstern JL, Hong G, Gee AD, Brown J (2005) Evidence for the presence of three distinct binding sites for the thioflavin T class of Alzheimer's disease PET imaging agents on beta-amyloid peptide fibrils. J Biol Chem 280:7677–7684CrossRefPubMed
42.
McKeith IG, Ballard CG, Perry RH, Ince PG, O’Brien JT, Neill D, Lowery K, Jaros E, Barber R, Thompson P, Swann A, Fairbairn AF, Perry EK (2000) Prospective validation of consensus criteria for the diagnosis of dementia with lewy bodies. Neurology 54(5):1050–1058CrossRefPubMed
43.
Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van Belle G, Berg L (1991) The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 41:479–486CrossRefPubMed
44.
Moossy J, Zubenko GS, Martinez AJ, Rao GR (1988) Bilateral symmetry of morphologic lesions in Alzheimer's disease. Arch Neurol 45:251–254CrossRefPubMed
45.
Murray ME, Lowe VJ, Graff-Radford NR, Liesinger AM, Cannon A, Przybelski SA, Rawal B, Parisi JE, Petersen RC, Kantarci K, Ross OA, Duara R, Knopman DS, Jack CR Jr, Dickson DW (2015) Clinicopathologic and 11C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer's disease spectrum. Brain 138:1370–1381CrossRefPubMedPubMedCentral
46.
47.
Nelissen N, Van LK, Thurfjell L, Owenius R, Vandenbulcke M, Koole M, Bormans G, Brooks DJ, Vandenberghe R (2009) Phase 1 study of the Pittsburgh compound B derivative 18 F-flutemetamol in healthy volunteers and patients with probable Alzheimer disease. J Nucl Med 50:1251–1259CrossRefPubMed
48.
Raji CA, Becker JT, Tsopelas ND, Price JC, Mathis CA, Saxton JA, Lopresti BJ, Hoge JA, Ziolko SK, DeKosky ST, Klunk WE (2008) Characterizing regional correlation, laterality and symmetry of amyloid deposition in mild cognitive impairment and Alzheimer’s disease with Pittsburgh Compound B. J Neurosci Methods 172:277–282CrossRefPubMedPubMedCentral
49.
50.
Rinne JO, Frantzen J, Leinonen V, Lonnrot K, Laakso A, Virtanen KA, Solin O, Kotkansalo A, Koivisto A, Sajanti J, Karppinen A, Lehto H, Rummukainen J, Buckley C, Smith A, Jones PA, Sherwin P, Farrar G, McLain R, Kailajarvi M, Grachev ID (2013) Prospective flutemetamol positron emission tomography and histopathology in normal pressure hydrocephalus. Neurodegener Dis 13:237–245PubMed
51.
Rinne JO, Wong DF, Wolk DA, Leinonen V, Arnold SE, Buckley C, Smith A, McLain R, Sherwin PF, Farrar G, Kailajarvi M, Grachev ID (2012) [(18)F] Flutemetamol PET imaging and cortical biopsy histopathology for fibrillar amyloid beta detection in living subjects with normal pressure hydrocephalus: pooled analysis of four studies. Acta Neuropathol 124:833–845CrossRefPubMed
52.
Rosenberg PB, Wong DF, Edell SL, Ross JS, Joshi AD, Brasic JR, Zhou Y, Raymont V, Kumar A, Ravert HT, Dannals RF, Pontecorvo MJ, Skovronsky DM, Lyketsos CG (2013) Cognition and amyloid load in Alzheimer disease imaged with florbetapir F 18(AV-45) positron emission tomography. Am J Geriatr Psychiatry 21:272–278CrossRefPubMedPubMedCentral
53.
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 68:232–240PubMedPubMedCentral
54.
55.
Thal DR, Beach TG, Zanette M, Heurling K, Chakrabarty A, Ismail A, Smith AP, Buckley C (2015) [(18)F] flutemetamol amyloid positron emission tomography in preclinical and symptomatic Alzheimer's disease: Specific detection of advanced phases of amyloid-beta pathology. Alzheimers Dement 11:975–985CrossRefPubMed
56.
Thal DR, Ghebremedhin E, Orantes M, Wiestler OD (2003) Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline. J Neuropathol Exp Neurol 62:1287–1301CrossRefPubMed
57.
Thal DR, Ghebremedhin E, Rub U, Yamaguchi H, Del TK, Braak H (2002) Two types of sporadic cerebral amyloid angiopathy. J Neuropathol Exp Neurol 61:282–293CrossRefPubMed
58.
Thal DR, Rub U, Orantes M, Braak H (2002) Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 58:1791–1800CrossRefPubMed
59.
Thurfjell L, Lilja J, Lundqvist R, Buckley C, Smith A, Vandenberghe R, Sherwin P (2014) Automated quantification of 18 F-flutemetamol PET activity for categorizing scans as negative or positive for brain amyloid: concordance with visual image reads. J Nucl Med 55:1623–1628CrossRefPubMed
60.
Vemuri P, Whitwell JL, Kantarci K, Josephs KA, Parisi JE, Shiung MS, Knopman DS, Boeve BF, Petersen RC, Dickson DW, Jack CR Jr (2008) Antemortem MRI based STructural Abnormality iNDex (STAND)-scores correlate with postmortem Braak neurofibrillary tangle stage. Neuroimage 42:559–567CrossRefPubMedPubMedCentral
61.
Villemagne VL, Klunk WE, Mathis CA, Rowe CC, Brooks DJ, Hyman BT, Ikonomovic MD, Ishii K, Jack CR, Jagust WJ, Johnson KA, Koeppe RA, Lowe VJ, Masters CL, Montine TJ, Morris JC, Nordberg A, Petersen RC, Reiman EM, Selkoe DJ, Sperling RA, Van LK, Weiner MW, Drzezga A (2012) Abeta Imaging: feasible, pertinent, and vital to progress in Alzheimer's disease. Eur J Nucl Med Mol Imaging 39:209–219CrossRefPubMedPubMedCentral
62.
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 80:998–1001CrossRefPubMed
63.
64.
Vonsattel JP, Myers RH, Hedley-Whyte ET, Ropper AH, Bird ED, Richardson EP Jr (1991) Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann Neurol 30:637–649CrossRefPubMed
65.
Wolk DA, Grachev ID, Buckley C, Kazi H, Grady MS, Trojanowski JQ, Hamilton RH, Sherwin P, McLain R, Arnold SE (2011) Association between in vivo fluorine 18-labeled flutemetamol amyloid positron emission tomography imaging and in vivo cerebral cortical histopathology. Arch Neurol 68:1398–1403CrossRefPubMedPubMedCentral
66.
Wolk DA, Zhang Z, Boudhar S, Clark CM, Pontecorvo MJ, Arnold SE (2012) Amyloid imaging in Alzheimer's disease: comparison of florbetapir and Pittsburgh compound-B positron emission tomography. J Neurol Neurosurg Psychiatry 83:923–926CrossRefPubMedPubMedCentral
67.
Wong DF, Moghekar AR, Rigamonti D, Brasic JR, Rousset O, Willis W, Buckley C, Smith A, Gok B, Sherwin P, Grachev ID (2013) An in vivo evaluation of cerebral cortical amyloid with [18 F] flutemetamol using positron emission tomography compared with parietal biopsy samples in living normal pressure hydrocephalus patients. Mol Imaging Biol 15:230–237CrossRefPubMedPubMedCentral
68.
Yamada M (2003) Senile Dementia of the Neurofibrillary Tangle Type (tangle-Only Dementia): Neuropathological Criteria and Clinical Guidelines for Diagnosis. Neuropathology 23(4):311–317CrossRefPubMed
69.
Yamaguchi H, Nakazato Y, Hirai S, Shoji M, Harigaya Y (1989) Electron micrograph of diffuse plaques. Initial stage of senile plaque formation in the Alzheimer brain. Am J Pathol 135:593–597PubMedPubMedCentral
70.
Ye L, Velasco A, Fraser G, Beach TG, Sue L, Osredkar T, Libri V, Spillantini MG, Goedert M, Lockhart A (2008) In vitro high affinity alpha-synuclein binding sites for the amyloid imaging agent PIB are not matched by binding to Lewy bodies in postmortem human brain. J Neurochem 105:1428–1437CrossRefPubMedPubMedCentral
Metadata
Title
Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injection
Authors
Milos D. Ikonomovic
Chris J. Buckley
Kerstin Heurling
Paul Sherwin
Paul A. Jones
Michelle Zanette
Chester A. Mathis
William E. Klunk
Aruna Chakrabarty
James Ironside
Azzam Ismail
Colin Smith
Dietmar R. Thal
Thomas G. Beach
Gill Farrar
Adrian P. L. Smith
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Acta Neuropathologica Communications / Issue 1/2016
Electronic ISSN: 2051-5960
DOI
https://doi.org/10.1186/s40478-016-0399-z

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