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Early AD pathology in a [C-11]PiB-negative case: a PiB-amyloid imaging, biochemical, and immunohistochemical study

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Abstract

Amyloid-β (Aβ) deposits are detectable in the brain in vivo using positron emission tomography (PET) and [C-11]-labeled Pittsburgh Compound B ([C-11]PiB); however, the sensitivity of this technique is not well understood. In this study, we examined Aβ pathology in an individual who had clinical diagnoses of probable dementia with Lewy bodies and possible Alzheimer’s disease (AD) but with no detectable [C-11]PiB PET retention ([C-11]PiB(−)) when imaged 17 months prior to death. Brain samples were processed in parallel with region-matched samples from an individual with a clinical diagnosis of probable AD and a positive [C-11]PiB PET scan ([C-11]PiB(+)) when imaged 10 months prior to death. In the [C-11]PiB(−) case, Aβ plaques were sparse, occupying less than 2% cortical area, and were weakly labeled with 6-CN-PiB, a highly fluorescent derivative of PiB. In contrast, Aβ plaques occupied up to 12% cortical area in the [C-11]PiB(+) case, and were intensely labeled with 6-CN-PIB. The [C-11]PiB(−) case had low levels of [H-3]PiB binding (<100 pmol/g) and Aβ1–42 (<500 pmol/g) concentration except in the frontal cortex where Aβ1–42 values (788 pmol/g) approached cortical values in the [C-11]PiB(+) case (800–1,700 pmol/g). In several cortical regions of the [C-11]PiB(−) case, Aβ1–40 levels were within the range of cortical Aβ1–40 values in the [C-11]PiB(+) case. Antemortem [C-11]PiB DVR values correlated well with region-matched postmortem measures of Aβ1–42 and Aβ1–40 in the [C-11]PiB(+), and with Aβ1–42 only in the [C-11]PiB(−) case. The low ratios of [H-3]PiB binding levels to Aβ concentrations and 6-CN-PiB to Aβ plaque loads in the [C-11]PiB(−) case indicate that Aβ pathology in the brain may be associated with low or undetectable levels of [C-11]PiB retention. Studies in greater numbers of [C-11]PiB PET autopsy cases are needed to define the Aβ concentration and [H-3]PiB binding levels required to produce a positive [C-11]PiB PET signal.

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Abbreviations

Aβ:

Amyloid-β

AD:

Alzheimer’s disease

[C-11]PiB:

Carbon 11-labeled Pittsburgh Compound B

CDR:

Clinical dementia rating

CAA:

Cerebral amyloid angiopathy

DLB:

Dementia with Lewy bodies

DVR:

Distribution volume ratio

ELISA:

Enzyme linked immunosorbant assay

IHC:

Immunohistochemistry

NFT:

Neurofibrillary tangles

MMSE:

Mini-Mental State Examination

MR:

Magnetic resonance

PiB:

Pittsburgh Compound B

PET:

Positron emission tomography

References

  1. Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND, Ziolko SK, James JA, Snitz BE, Houck PR, Bi W, Cohen AD, Lopresti BJ, DeKosky ST, Halligan EM, Klunk WE (2008) Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol 65:1509–1517

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  3. Bouras C, Hof PR, Giannakopoulos P, Michel JP, Morrison JH (1994) Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of elderly patients: a quantitative evaluation of a one-year autopsy population from a geriatric hospital. Cereb Cortex 4:138–150

    Article  PubMed  CAS  Google Scholar 

  4. Braak H, Braak E (1997) Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging 18:351–357

    Article  PubMed  CAS  Google Scholar 

  5. 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 74:77–84

    Article  PubMed  CAS  Google Scholar 

  6. Cairns NJ, Ikonomovic MD, Benzinger T, Storandt M, Fagan AM, Shah A, Schmidt RE, Perry A, 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. Arch Neurol 66:1557–1562

    Article  PubMed  Google Scholar 

  7. Clark CM, Ewbank D, Lerner A, Doody R, Henderson VW, Panisset M, Morris JC, Fillenbaum GG, Heyman A (1997) The relationship between extrapyramidal signs and cognitive performance in patients with Alzheimer’s disease enrolled in the CERAD Study. Consortium to Establish a Registry for Alzheimer’s Disease. Neurology 49:70–75

    PubMed  CAS  Google Scholar 

  8. Consensus (1998) Consensus report of the Working Group on “Molecular and Biochemical Markers of Alzheimer’s Disease”. The Ronald and Nancy Reagan Research Institute of the Alzheimer’s Association and the National Institute on Aging Working Group. Neurobiol Aging 19:109–116

  9. Davies L, Wolska B, Hilbich C, Multhaup G, Martins R, Simms G, Beyreuther K, Masters CL (1988) A4 amyloid protein deposition and the diagnosis of Alzheimer’s disease: prevalence in aged brains determined by immunocytochemistry compared with conventional neuropathologic techniques. Neurology 38:1688–1693

    PubMed  CAS  Google Scholar 

  10. Dickson DW (1997) The pathogenesis of senile plaques. J Neuropathol Exp Neurol 56:321–339

    Article  PubMed  CAS  Google Scholar 

  11. Fujishiro H, Ferman TJ, Boeve BF, Smith GE, Graff-Radford NR, Uitti RJ, Wszolek ZK, Knopman DS, Petersen RC, Parisi JE, Dickson DW (2008) Validation of the neuropathologic criteria of the third consortium for dementia with Lewy bodies for prospectively diagnosed cases. J Neuropath Exp Neurol 67:649–656

    Article  PubMed  Google Scholar 

  12. Harigaya Y, Saido TC, Eckman CB, Prada CM, Shoji M, Younkin SG (2000) Amyloid beta protein starting pyroglutamate at position 3 is a major component of the amyloid deposits in the Alzheimer’s disease brain. Biochem Biophys Res Commun 276:422–427

    Article  PubMed  CAS  Google Scholar 

  13. Haroutunian V, Perl DP, Purohit DP, Marin D, Khan K, Lantz M, Davis KL, Mohs RC (1998) Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease. Arch Neurol 55:1185–1191

    Article  PubMed  CAS  Google Scholar 

  14. Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression, and mortality. Neurology 17:427–442

    PubMed  CAS  Google Scholar 

  15. Ikonomovic MD, Abrahamson EE, Isanski BA, Debnath ML, Mathis CA, DeKosky ST, Klunk WE (2006) X-34 labeling of abnormal protein aggregates during the progression of Alzheimer’s disease. Methods Enzymol 412:123–144

    Article  PubMed  CAS  Google Scholar 

  16. 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 131:1630–1645

    Article  PubMed  Google Scholar 

  17. Kadir A, Marutle A, Gonzalez D, Schöll 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 134:301–317

    Article  PubMed  Google Scholar 

  18. Kamal A, Almenar-Queralt A, LeBlanc JF, Roberts EA, Goldstein LS (2001) Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature 414:643–648

    Article  PubMed  CAS  Google Scholar 

  19. Kantarci K, Yang C, Schneider JA, Senjem ML, Reyes DA, Lowe VJ, Barnes LL, Aggarwal NT, Bennett DA, Smith GE, Petersen RC, Jack CRJ, Boeve BF (2010) Ante mortem amyloid imaging and β-amyloid pathology in a case with dementia with Lewy bodies. Neurobiol Aging [Epub ahead of print]

  20. Khachaturian ZS (1985) Diagnosis of Alzheimer’s disease. Arch Neurol 42:1097–1105

    Article  PubMed  CAS  Google Scholar 

  21. Kim KS (1988) Production and characterization of monoclonal antibodies reactive to synthetic cerebrovascular amyloid peptide. Neurosci Res Comm 2:121–130

    CAS  Google Scholar 

  22. Kim K, Wen G, Bancher C et al (1990) Detection and quantitation of β-peptide with two monoclonal antibodies. Neurosci Res Commun 7:113–122

    CAS  Google Scholar 

  23. Klunk WE, Wang Y, Huang GF, Debnath ML, Holt DP, Mathis CA (2001) Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain. Life Sci 69:1471–1484

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  25. Lalowski M, Golabek A, Lemere CA, Selkoe DJ, Wisniewski HM, Beavis RC, Frangione B, Wisniewski T (1996) The “nonamyloidogenic” p3 fragment (amyloid beta17–42) is a major constituent of Down’s syndrome cerebellar preamyloid. J Biol Chem 271:33623–33631

    Article  PubMed  CAS  Google Scholar 

  26. Leinonen V, Alafuzoff I, Aalto S, Suotunen T, Savolainen S, Någren K, Tapiola T, Pirttilä T, Rinne J, Jääskeläinen 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 65:1304–1309

    Article  PubMed  Google Scholar 

  27. 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 130:2607–2615

    Google Scholar 

  28. Logan J, Fowler JS, Volkow ND, Wang GJ, Ding YS, Alexoff DL (1996) Distribution volume ratios without blood sampling from graphical analysis of PET data. J Cereb Blood Flow Metab 16:834–840

    Article  PubMed  CAS  Google Scholar 

  29. Lopresti BJ, Klunk WE, Mathis CA, Hoge JA, Ziolko SK, Lu X, Meltzer CC, Schimmel K, Tsopelas ND, DeKosky ST, Price JC (2005) Simplified quantification of Pittsburgh Compound B amyloid imaging PET studies: a comparative analysis. J Nucl Med 46:1959–1972

    PubMed  CAS  Google Scholar 

  30. Maeda J, Ji B, Irie T, Tomiyama T, Maruyama M, Okauchi T, Staufenbiel M, Iwata N, Ono M, Saido TC, Suzuki K, Mori H, Higuchi M, Suhara T (2007) Longitudinal, quantitative assessment of amyloid, neuroinflammation, and anti-amyloid treatment in a living mouse model of Alzheimer’s disease enabled by positron emission tomography. J Neurosci 27:10957–10968

    Article  PubMed  CAS  Google Scholar 

  31. Mathis CA, Bacskai BJ, Kajdasz ST, McLellan ME, Frosch MP, Hyman BT, Holt DP, Wang Y, Huang GF, Debnath ML, Klunk WE (2002) A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain. Bioorg Med Chem Lett 12:295–298

    Article  PubMed  CAS  Google Scholar 

  32. Mathis CA, Wang Y, Holt DP, Huang GF, Debnath ML, Klunk WE (2003) Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. J Med Chem 46:2740–2754

    Article  PubMed  CAS  Google Scholar 

  33. McKeith IG (2006) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop. J Alzheimer Dis 9:417–423

    Google Scholar 

  34. Mintun MA, Raichle ME, Kilbourn MR, Wooten GF, Welch MJ (1984) A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography. Ann Neurol 15:217–227

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  36. 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 41:479–486

    PubMed  CAS  Google Scholar 

  37. Morris JC, Roe CM, Xiong C, Fagan AM, Goate AM, Holtzman DM, Mintun MA (2010) APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Ann Neurol 67:122–131

    Article  PubMed  CAS  Google Scholar 

  38. 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 25:1528–1547

    Article  PubMed  CAS  Google Scholar 

  39. Price JL, Morris JC (1999) Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol 45:358–368

    Article  PubMed  CAS  Google Scholar 

  40. Price JL, McKeel DWJ, Buckles VD, Roe CM, Xiong C, Grundman M, Hansen LA, Petersen RC, Parisi JE, Dickson DW, Smith CD, Davis DG, Schmitt FA, Markesbery WR, Kaye J, Kurlan R, Hulette C, Kurland BF, Higdon R, Kukull W, Morris JC (2009) Neuropathology of nondemented aging: Presumptive evidence for preclinical Alzheimer disease. Neurobiol Aging 30:1026–1036

    Article  PubMed  Google Scholar 

  41. Roe CM, Mintun MA, D’Angelo G, Xiong C, Grant EA, Morris JC (2008) Alzheimer disease and cognitive reserve: variation of education effect with carbon 11-labeled Pittsburgh Compound B uptake. Arch Neurol 65:1467–1471

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  43. 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 68:1718–1725

    Article  PubMed  CAS  Google Scholar 

  44. Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, Jones G, Fripp J, Tochon-Danguy H, Morandeau L, O’Keefe G, Price R, Raniga P, Robins P, Acosta O, Lenzo N, Szoeke C, Salvado O, Head R, Martins R, Masters CL, Ames D, Villemagne VL (2010) Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging 31:1275–1283

    Article  PubMed  Google Scholar 

  45. Saido TC, Iwatsubo T, Mann DM, Shimada H, Ihara Y, Kawashima S (1995) Dominant and differential deposition of distinct beta-amyloid peptide species, A beta N3(pE), in senile plaques. Neuron 14:457–466

    Article  PubMed  CAS  Google Scholar 

  46. 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 68:232–240

    Article  PubMed  Google Scholar 

  47. Styren SD, Hamilton RL, Styren GC, Klunk WE (2000) X-34, a fluorescent derivative of Congo red: a novel histochemical stain for Alzheimer’s disease pathology. J Histochem Cytochem 48:1223–1232

    Article  PubMed  CAS  Google Scholar 

  48. Thompson PW, Ye L, Morgenstern JL, Sue L, Beach TG, Judd DJ, Shipley NJ, Libri V, Lockhart A (2009) Interaction of the amyloid imaging tracer FDDNP with hallmark Alzheimer’s disease pathologies. J Neurochem 109:623–630

    Article  PubMed  CAS  Google Scholar 

  49. 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 80:998–1001

    Article  PubMed  CAS  Google Scholar 

  50. Wolf DS, Gearing M, Snowdon DA, Mori H, Markesbery WR, Mirra SS (1999) Progression of regional neuropathology in Alzheimer disease and normal elderly: findings from the Nun study. Alzheimer Dis Assoc Disord 13:226–231

    Article  PubMed  CAS  Google Scholar 

  51. Wu Y, Carson RE (2002) Noise reduction in the simplified reference tissue model for neuroreceptor functional imaging. J Cereb Blood Flow Metab 22:1440–1452

    Article  PubMed  Google Scholar 

  52. Yamamoto T, Hirano A (1986) A comparative study of modified Bielschowsky, Bodian and thioflavin S stains on Alzheimer’s neurofibrillary tangles. Neuropathol Appl Neurobiol 12:3–9

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We gratefully acknowledge the technical expertise of Suganya Srinivasan, Lan Shao, Hui Wang, and Jonette Werley. We thank the staff at the University of Pittsburgh Alzheimer’s Disease Research Center and PET facility for their efforts in conducting and analyzing these studies. We are indebted to our subjects and their families for the selfless contributions that made this work possible. This work was supported by the National Institutes of Health grants AG025204, AG025516, AG005133, AG014449, and AG033042, GE Healthcare, The Phillip V. and Anna S. Brown Foundation, and the Snee-Reinhardt Charitable Foundation.

Conflict of interest

GE Healthcare holds a license agreement with the University of Pittsburgh based on the technology described in this manuscript. Drs. Klunk and Mathis are co-inventors of PiB and therefore have a financial interest in this license agreement. GE Healthcare provided a portion of the grant support for the [C-11]PiB brain autopsy program but, like other funding agencies, had no role in the design or interpretation of results or preparation of this manuscript.

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Authors and Affiliations

  1. Department of Neurology, University of Pittsburgh School of Medicine, 200 Lothrop Street BST S521, Pittsburgh, PA, 15213, USA

    Milos D. Ikonomovic, Eric E. Abrahamson, William R. Paljug, Oscar L. Lopez & William E. Klunk

  2. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Milos D. Ikonomovic, Manik L. Debnath, Anne D. Cohen & William E. Klunk

  3. Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Julie C. Price & Chester A. Mathis

  4. Department of Neuropathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Ronald L. Hamilton

  5. Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, Pittsburgh, PA, USA

    Milos D. Ikonomovic

  6. Department of Psychiatry, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan

    Katsuyoshi Mizukami

  7. Office of the Dean and Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA, USA

    Steven T. DeKosky

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  1. Milos D. Ikonomovic
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Correspondence to Milos D. Ikonomovic.

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Supplemental Fig. 1 Morphological classification of Aβ and X-34 positive plaques

Photomicrographs illustrate the morphology of Aβ amyloid deposits in adjacent pairs (a-b and c-d) of 6 μm paraffin sections of the frontal cortex from the [C-11]PiB(+) case, processed for Aβ immunohistochemistry with hematoxylin counterstaining (a and c) or X-34 histofluorescence (b and d). Plaques were classified as diffuse (large empty arrow in a-b), primitive (single thin arrow in a-b), classic (small empty arrow in c-d), or burnt out (double arrow in a-b). Cerebral amyloid angiopathy (CAA) is marked with an asterisk in a-b and c-d. An example of X-34 labeled neurofibrillary tangles is shown in the inset (b). Scale bar = 75 μm.

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Ikonomovic, M.D., Abrahamson, E.E., Price, J.C. et al. Early AD pathology in a [C-11]PiB-negative case: a PiB-amyloid imaging, biochemical, and immunohistochemical study. Acta Neuropathol 123, 433–447 (2012). https://doi.org/10.1007/s00401-012-0943-2

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