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In Vitro Imaging Techniques in Neurodegenerative Diseases

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Abstract

Neurodegeneration induces various changes in the brain, changes that may be investigated using neuroimaging techniques. The in vivo techniques are useful for the visualization of major changes, and the progressing abnormalities may also be followed longitudinally. However, to study and quantify minor abnormalities, neuroimaging of postmortem brain tissue is used. These in vitro methods are complementary to the in vivo techniques and contribute to the knowledge of pathophysiology and etiology of the neurodegenerative diseases. In vitro radioligand autoradiography has given great insight in the involvement of different neuronal receptor systems in these diseases. Data on the dopamine and cholinergic systems in neurodegeneration are discussed in this review. Also, the amyloid plaques are studied using in vitro radioligand autoradiography. Using one of the newer methods, imaging matrix-assisted laser desorption ionization mass spectrometry, the distribution of a large number of peptides and proteins may be detected in vitro on brain cryosections. In this overview, we describe in vitro imaging techniques in the neurodegenerative diseases as a complement to in vivo positron emission tomography and single photon emission computed tomography imaging.

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References

  1. Maurer K, Volk S, Gerbaldo H (1997) Auguste D and Alzheimer’s disease. Lancet 349:1546–1549

    Article  PubMed  CAS  Google Scholar 

  2. Alzheimer A (1907) About a peculiar disease of the cerebral cortex. Alzheimer Dis Assoc Disord 1:3–8 (translated by L. Jarvik and H. Greenson, 1987)

    Google Scholar 

  3. Braak H, Braak E (1995) Staging of Alzheimer’s disease-related neurofibrillary changes. Neurobiol Aging 16:271–278; discussion 278–284

    Article  PubMed  CAS  Google Scholar 

  4. Braak H, de Vos RA, Jansen EN, Bratzke H, Braak E (1998) Neuropathological hallmarks of Alzheimer’s and Parkinson’s diseases. Prog Brain Res 117:267–285

    Article  PubMed  CAS  Google Scholar 

  5. Ingelsson M, Fukumoto H, Newell KL, et al. (2004) Early Ab accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain. Neurology 62:925–931

    PubMed  CAS  Google Scholar 

  6. Schonheit B, Zarski R, Ohm TG (2004) Spatial and temporal relationships between plaques and tangles in Alzheimer-pathology. Neurobiol Aging 25:697–711

    Article  PubMed  Google Scholar 

  7. Onorato JM, Thorpe SR, Baynes JW (1998) Immunohistochemical and ELISA assays for biomarkers of oxidative stress in aging and disease. Ann NY Acad Sci 854:277–290

    Article  PubMed  CAS  Google Scholar 

  8. Ulrich J (1993) Histochemistry and immunohistochemistry of Alzheimer’s disease. Prog Histochem Cytochem 27:1–63

    PubMed  CAS  Google Scholar 

  9. Scheff SW, Price DA (2003) Synaptic pathology in Alzheimer’s disease: a review of ultrastructural studies. Neurobiol Aging 24:1029–1046

    Article  PubMed  CAS  Google Scholar 

  10. Harris JE, Sloane JF, King DT (1950) New techniques in autoradiography. Nature 166:25–26

    Article  PubMed  CAS  Google Scholar 

  11. Ullberg S, Larsson B (1981) Whole-body autoradiography. Methods Enzymol 77:64–80

    PubMed  CAS  Google Scholar 

  12. Ullberg S (1977) The technique of whole body autoradiography. Cryosectioning of large specimens. Sci Tools (The LKB Instrument J) 1–29

  13. Chaurand P, Schwartz SA, Caprioli RM (2004) Assessing protein patterns in disease using imaging mass spectrometry. J Proteome Res 3:245–252

    Article  PubMed  CAS  Google Scholar 

  14. Reyzer ML, Caprioli RM (2005) MALDI mass spectrometry for direct tissue analysis: a new tool for biomarker discovery. J Proteome Res 4:1138–1142

    Article  PubMed  CAS  Google Scholar 

  15. Rofina JE, Singh K, Skoumalova-Vesela A, et al. (2004) Histochemical accumulation of oxidative damage products is associated with Alzheimer-like pathology in the canine. Amyloid 11:90–100

    PubMed  CAS  Google Scholar 

  16. Inglefield JR, Schwartz-Bloom RD (1999) Fluorescence imaging of changes in intracellular chloride in living brain slices. Methods 18:197–203

    Article  PubMed  CAS  Google Scholar 

  17. Brendza RP, Simmons K, Bales KR, Paul SM, Goldberg MP, Holtzman DM (2003) Use of YFP to study amyloid-beta associated neurite alterations in live brain slices. Neurobiol Aging 24:1071–1077

    Article  PubMed  CAS  Google Scholar 

  18. Hintersteiner M, Enz A, Frey P, et al. (2005) In vivo detection of amyloid-β deposits by near-infrared imaging using an oxazine-derivative probe. Nat Biotechnol 23:577–583

    Article  PubMed  CAS  Google Scholar 

  19. Hall H, Hurd Y, Pauli S, Halldin C, Sedvall G (2001) Human brain imaging post-mortem—whole hemisphere technologies. Int Rev Psychiatry Res Methods Biol Psychiatry 13:12–17

    CAS  Google Scholar 

  20. Bergström M, Awad R, Estrada S, et al. (2003) Autoradiography with positron emitting isotopes in positron emission tomography tracer discovery. Mol Imaging Biol 5:390–396

    Article  PubMed  Google Scholar 

  21. Sihver W, Sihver S, Bergström M, et al. (1997) Methodological aspects for in vitro characterization of receptor binding using 11C-labeled receptor ligands: a detailed study with the benzodiazepine receptor antagonist [11C]Ro 15-1788. Nucl Med Biol 24:723–731

    Article  PubMed  CAS  Google Scholar 

  22. Sihver S, Sihver W, Bergström M, et al. (1999) Quantitative autoradiography with short-lived positron emission tomography tracers: a study on muscarinic acetylcholine receptors with N-[11C]methyl-4-piperidylbenzilate. J Pharmacol Exp Ther 290:917–922

    PubMed  CAS  Google Scholar 

  23. Johnston RF, Pickett SC, Barker DL (1990) Autoradiography using storage phosphor technology. Electrophoresis 11:355–360

    Article  PubMed  CAS  Google Scholar 

  24. Charpak G, Dominik W, Zaganidis N (1989) Optical imaging of the spatial distribution of beta-particles emerging from surfaces. Proc Natl Acad Sci U S A 86:1741–1745

    Article  PubMed  CAS  Google Scholar 

  25. Langlois X, te Riele P, Wintmolders C, Leysen JE, Jurzak M (2001) Use of the β-imager for rapid ex vivo autoradiography exemplified with central nervous system penetrating neurokinin 3 antagonists. J Pharmacol Exp Ther 299:712–717

    PubMed  CAS  Google Scholar 

  26. Hall H, Halldin C, Farde L, Sedvall G (1998) Whole hemisphere autoradiography of the postmortem human brain. Nucl Med Biol 25:715–719

    Article  PubMed  CAS  Google Scholar 

  27. Quirion R, Robitaille Y, Martial J, et al. (1987) Human brain receptor autoradiography using whole hemisphere sections: a general method that minimizes tissue artefacts. Synapse 1:446–454

    Article  PubMed  CAS  Google Scholar 

  28. Persson A, d’Argy R, Gillberg PG, et al. (1991) Autoradiography with saturation experiments of 11C-Ro 15-1788 binding to human brain sections. J Neurosci Methods 36:53–61

    Article  PubMed  CAS  Google Scholar 

  29. Caberlotto L, Fuxe K, Sedvall G, Hurd YL (1997) Localization of neuropeptide Y Y1 mRNA in the human brain: abundant expression in cerebral cortex and striatum. Eur J Neurosci 9:1212–1225

    Article  PubMed  CAS  Google Scholar 

  30. Sköld K, Svensson M, Kaplan A, Björkesten L, Åström J, Andrén PE (2002) A neuroproteomic approach to targeting neuropeptides in the brain. Proteomics 2:447–454

    Article  PubMed  Google Scholar 

  31. Svensson M, Sköld K, Svenningsson P, Andrén PE (2003) Peptidomics-based discovery of novel neuropeptides. J Proteome Res 2:213–219

    Article  PubMed  CAS  Google Scholar 

  32. Wong DF, Pomper MG (2003) Predicting the success of a radiopharmaceutical for in vivo imaging of central nervous system neuroreceptor systems. Mol Imaging Biol 5:350–362

    Article  PubMed  Google Scholar 

  33. Hall H, Köhler C, Gawell L, Farde L, Sedvall G (1988) Raclopride, a new selective ligand for the dopamine-D2 receptors. Prog Neuropsychopharmacol Biol Psychiatry 12:559–568

    Article  PubMed  CAS  Google Scholar 

  34. Farde L, Hall H, Ehrin E, Sedvall G (1986) Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science 231:258–261

    Article  PubMed  CAS  Google Scholar 

  35. Farde L, Ehrin E, Eriksson L, et al. (1985) Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography. Proc Natl Acad Sci U S A 82:3863–3867

    Article  PubMed  CAS  Google Scholar 

  36. Halldin C, Farde L, Högberg T, et al. (1995) Carbon-11-FLB 457: a radioligand for extrastriatal D2 dopamine receptors. J Nucl Med 36:1275–1281

    PubMed  CAS  Google Scholar 

  37. Hall H, Farde L, Halldin C, Hurd YL, Pauli S, Sedvall G (1996) Autoradiographic localization of extrastriatal D2-dopamine receptors in the human brain using [125I]epidepride. Synapse 23:115–123

    Article  PubMed  CAS  Google Scholar 

  38. Matsumura K, Bergström M, Onoe H, et al. (1995) In vitro positron emission tomography (PET): use of positron emission tracers in functional imaging in living brain slices. Neurosci Res 22:219–229

    Article  PubMed  CAS  Google Scholar 

  39. Ogawa M, Watabe H, Teramoto N, et al. (2005) Understanding of cerebral energy metabolism by dynamic living brain slice imaging system with [18F]FDG. Neurosci Res 52:357–361

    Article  PubMed  CAS  Google Scholar 

  40. Lindhe O, Skogseid B, Brandt I (2002) Cytochrome P450-catalyzed binding of 3-methylsulfonyl-DDE and o,p′-DDD in human adrenal zona fasciculata/reticularis. J Clin Endocrinol Metab 87:1319–1326

    Article  PubMed  CAS  Google Scholar 

  41. Brendel K, McKee RL, Hruby VJ, Jonson DG, Gandolfi AJ, Krumdieck CL (1987) Precision cut tissue slices in culture. A new tool in pharmacology. Proc West Pharmacol Soc 291–293

  42. Bach PH, Vickers AEM, Fisher R, et al. (1996) The use of tissue slices for pharmacotoxicology studies. The report and recommendations of ECVAM Workshop Report 20. ATLA 24:893–923

    Google Scholar 

  43. Sihver S, Marklund N, Hillered L, Långström B, Watanabe Y, Bergström M (2001) Changes in mACh, NMDA and GABAA receptor binding after lateral fluid-percussion injury: in vitro autoradiography of rat brain frozen sections. J Neurochem 78:417–423

    Article  PubMed  CAS  Google Scholar 

  44. Ishiwata K, Ogi N, Hayakawa N, et al. (2002) Positron emission tomography and ex vivo and in vitro autoradiography studies on dopamine D2-like receptor degeneration in the quinolinic acid-lesioned rat striatum: comparison of [11C]raclopride, [11C]nemonapride and [11C]N-methylspiperone. Nucl Med Biol 29:307–316

    Article  PubMed  CAS  Google Scholar 

  45. Wu F, Yngve U, Hedberg E, et al. (2000) Distribution of 76Br-labeled antisense oligonucleotides of different length determined ex vivo in rats. Eur J Pharm Sci 10:179–186

    Article  PubMed  CAS  Google Scholar 

  46. Garcia-Jimenez A, Cowburn RF, Ohm TG, Bogdanovic N, Winblad B, Fastbom J (1999) Quantitative autoradiography of [3H]forskolin binding sites in post-mortem brain staged for Alzheimer’s disease neurofibrillary changes and amyloid deposits. Brain Res 850:104–117

    Article  PubMed  CAS  Google Scholar 

  47. Garcia-Jimenez A, Cowburn RF, Ohm TG, et al. (2002) Loss of stimulatory effect of guanosine triphosphate on [35S]GTPgS binding correlates with Alzheimer’s disease neurofibrillary pathology in entorhinal cortex and CA1 hippocampal subfield. J Neurosci Res 67:388–398

    Article  PubMed  CAS  Google Scholar 

  48. Nordberg A (2004) PET imaging of amyloid in Alzheimer’s disease. Lancet Neurol 3:519–527

    Article  PubMed  CAS  Google Scholar 

  49. Klunk WE, Engler H, Nordberg A, et al. (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 55:306–319

    Article  PubMed  CAS  Google Scholar 

  50. Archer HA, Edison P, Brooks DJ, et al. (2006) Amyloid load and cerebral atrophy in Alzheimer’s disease: An 11C-PIB positron emission tomography study. Ann Neurol 60:145–147

    Article  PubMed  Google Scholar 

  51. Mintun MA, Larossa GN, Sheline YI, et al. (2006) [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology 67:446–452

    Article  PubMed  CAS  Google Scholar 

  52. Klunk WE, Lopresti BJ, Ikonomovic MD, et al. (2005) Binding of the positron emission tomography tracer Pittsburgh compound-B reflects the amount of amyloid-β in Alzheimer’s disease brain but not in transgenic mouse brain. J Neurosci 25:10598–10606

    Article  PubMed  CAS  Google Scholar 

  53. Klunk WE, Wang Y, Huang GF, et al. (2003) The binding of 2-(4′-methylaminophenyl)benzothiazole to postmortem brain homogenates is dominated by the amyloid component. J Neurosci 23:2086–2092

    PubMed  CAS  Google Scholar 

  54. Cai L, Chin FT, Pike VW, et al. (2004) Synthesis and evaluation of two 18F-labeled 6-iodo-2-(4′-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine derivatives as prospective radioligands for β-amyloid in Alzheimer’s disease. J Med Chem 47:2208–2218

    Article  PubMed  CAS  Google Scholar 

  55. Kung MP, Hou C, Zhuang ZP, Cross AJ, Maier DL, Kung HF (2004) Characterization of IMPY as a potential imaging agent for β-amyloid plaques in double transgenic PSAPP mice. Eur J Nucl Med Mol Imaging 31:1136–1145

    Article  PubMed  CAS  Google Scholar 

  56. Okamura N, Suemoto T, Furumoto S, et al. (2005) Quinoline and benzimidazole derivatives: candidate probes for in vivo imaging of tau pathology in Alzheimer’s disease. J Neurosci 25:10857–10862

    Article  PubMed  CAS  Google Scholar 

  57. Caulfield MP (1993) Muscarinic receptors—characterization, coupling and function. Pharmacol Ther 58:319–379

    Article  PubMed  CAS  Google Scholar 

  58. Paterson D, Nordberg A (2000) Neuronal nicotinic receptors in the human brain. Prog Neurobiol 61:75–111

    Article  PubMed  CAS  Google Scholar 

  59. Pereira EF, Hilmas C, Santos MD, Alkondon M, Maelicke A, Albuquerque EX (2002) Unconventional ligands and modulators of nicotinic receptors. J Neurobiol 53:479–500

    Article  PubMed  CAS  Google Scholar 

  60. Clementi F, Fornasari D, Gotti C (2000) Neuronal nicotinic acetylcholine receptors: from structure to therapeutics. Trends Pharmacol Sci 21:35–37

    Article  PubMed  CAS  Google Scholar 

  61. Karlin A (2002) Emerging structure of the nicotinic acetylcholine receptors. Nat Rev Neurosci 3:102–114

    Article  PubMed  CAS  Google Scholar 

  62. Dani JA (2001) Overview of nicotinic receptors and their roles in the central nervous system. Biol Psychiatry 49:166–174

    Article  PubMed  CAS  Google Scholar 

  63. Court JA, Martin-Ruiz C, Graham A, Perry E (2000) Nicotinic receptors in human brain: topography and pathology. J Chem Neuroanat 20:281–298

    Article  PubMed  CAS  Google Scholar 

  64. Spurden DP, Court JA, Lloyd S, et al. (1997) Nicotinic receptor distribution in the human thalamus: autoradiographical localization of [3H]nicotine and [125I]α-bungarotoxin binding. J Chem Neuroanat 13:105–113

    Article  PubMed  CAS  Google Scholar 

  65. Marutle A, Warpman U, Bogdanovic N, Nordberg A (1998) Regional distribution of subtypes of nicotinic receptors in human brain and effect of aging studied by (+/−)-[3H]epibatidine. Brain Res 801:143–149

    Article  PubMed  CAS  Google Scholar 

  66. Breese CR, Adams C, Logel J, et al. (1997) Comparison of the regional expression of nicotinic acetylcholine receptor α7 mRNA and [125I]-α-bungarotoxin binding in human postmortem brain. J Comp Neurol 387:385–398

    Article  PubMed  CAS  Google Scholar 

  67. Graham AJ, Ray MA, Perry EK, et al. (2003) Differential nicotinic acetylcholine receptor subunit expression in the human hippocampus. J Chem Neuroanat 25:97–113

    Article  PubMed  CAS  Google Scholar 

  68. Teaktong T, Graham A, Court J, et al. (2003) Alzheimer’s disease is associated with a selective increase in α7 nicotinic acetylcholine receptor immunoreactivity in astrocytes. Glia 41:207–211

    Article  PubMed  Google Scholar 

  69. Sihver W, Gillberg PG, Svensson AL, Nordberg A (1999) Autoradiographic comparison of [3H](−)nicotine, [3H]cytisine and [3H]epibatidine binding in relation to vesicular acetylcholine transport sites in the temporal cortex in Alzheimer’s disease. Neuroscience 94:685–696

    Article  PubMed  CAS  Google Scholar 

  70. Perry E, Martin-Ruiz C, Lee M, et al. (2000) Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy body diseases. Eur J Pharmacol 393:215–222

    Article  PubMed  CAS  Google Scholar 

  71. Hellström-Lindahl E, Mousavi M, Zhang X, Ravid R, Nordberg A (1999) Regional distribution of nicotinic receptor subunit mRNAs in human brain: comparison between Alzheimer and normal brain. Brain Res Mol Brain Res 66:94–103

    Article  PubMed  Google Scholar 

  72. Guan ZZ, Zhang X, Ravid R, Nordberg A (2000) Decreased protein levels of nicotinic receptor subunits in the hippocampus and temporal cortex of patients with Alzheimer’s disease. J Neurochem 74:237–243

    Article  PubMed  CAS  Google Scholar 

  73. Nordberg A (1999) PET studies and cholinergic therapy in Alzheimer’s disease. Rev Neurol (Paris) 155(Suppl 4):S53–S63

    Google Scholar 

  74. Nordberg A, Lundqvist H, Hartvig P, Lilja A, Långström B (1995) Kinetic analysis of regional (S)(−)11C-nicotine binding in normal and Alzheimer brains—in vivo assessment using positron emission tomography. Alzheimer Dis Assoc Disord 9:21–27

    Article  PubMed  CAS  Google Scholar 

  75. Perry EK, Martin-Ruiz CM, Court JA (2001) Nicotinic receptor subtypes in human brain related to aging and dementia. Alcohol 24:63–68

    Article  PubMed  CAS  Google Scholar 

  76. Mash DC, Flynn DD, Potter LT (1985) Loss of M2 muscarine receptors in the cerebral cortex in Alzheimer’s disease and experimental cholinergic denervation. Science 228:1115–1117

    Article  PubMed  CAS  Google Scholar 

  77. Nordberg A (1992) Neuroreceptor changes in Alzheimer disease. Cerebrovasc Brain Metab Rev 4:303–328

    PubMed  CAS  Google Scholar 

  78. Lai MK, Lai OF, Keene J, et al. (2001) Psychosis of Alzheimer’s disease is associated with elevated muscarinic M2 binding in the cortex. Neurology 57:805–811

    PubMed  CAS  Google Scholar 

  79. Warpman U, Alafuzoff I, Nordberg A (1993) Coupling of muscarinic receptors to GTP proteins in postmortem human brain—alterations in Alzheimer’s disease. Neurosci Lett 150:39–43

    Article  PubMed  CAS  Google Scholar 

  80. Tsang SW, Lai MK, Kirvell S, et al. (2006) Impaired coupling of muscarinic M1 receptors to G-proteins in the neocortex is associated with severity of dementia in Alzheimer’s disease. Neurobiol Aging 27:1216–1223

    Article  PubMed  CAS  Google Scholar 

  81. Kar S, Slowikowski SP, Westaway D, Mount HT (2004) Interactions between b-amyloid and central cholinergic neurons: implications for Alzheimer’s disease. J Psychiatry Neurosci 29:427–441

    PubMed  Google Scholar 

  82. Bannon MJ (2005) The dopamine transporter: role in neurotoxicity and human disease. Toxicol Appl Pharmacol 204:355–360

    Article  PubMed  CAS  Google Scholar 

  83. Marshall V, Grosset D (2003) Role of dopamine transporter imaging in routine clinical practice. Mov Disord 18:1415–1423

    Article  PubMed  Google Scholar 

  84. Marek K, Jennings D, Seibyl J (2003) Single-photon emission tomography and dopamine transporter imaging in Parkinson’s disease. Adv Neurol 91:183–191

    PubMed  Google Scholar 

  85. Prunier C, Payoux P, Guilloteau D, et al. (2003) Quantification of dopamine transporter by 123I-PE2I SPECT and the noninvasive Logan graphical method in Parkinson’s disease. J Nucl Med 44:663–670

    PubMed  CAS  Google Scholar 

  86. Tissingh G, Booij J, Bergmans P, et al. (1998) Iodine-123-N-omega-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl)tropane SPECT in healthy controls and early-stage, drug-naive Parkinson’s disease. J Nucl Med 39:1143–1148

    PubMed  CAS  Google Scholar 

  87. Tissingh G, Bergmans P, Booij J, et al. (1998) Drug-naive patients with Parkinson’s disease in Hoehn and Yahr stages I and II show a bilateral decrease in striatal dopamine transporters as revealed by [123I]β-CIT SPECT. J Neurol 245:14–20

    Article  PubMed  CAS  Google Scholar 

  88. Hall H, Halldin C, Guilloteau D, et al. (1999) Visualization of the dopamine transporter in the human brain postmortem with the new selective ligand [125I]PE2I. Neuroimage 9:108–116

    Article  PubMed  CAS  Google Scholar 

  89. Guilloteau D, Emond P, Baulieu JL, et al. (1998) Exploration of the dopamine transporter: in vitro and in vivo characterization of a high-affinity and high-specificity iodinated tropane derivative (E)-N-(3-iodoprop-2-enyl)-2β-carbomethoxy-3β-(4′-methylphenyl)nortropane (PE2I). Nucl Med Biol 25:331–337

    Article  PubMed  CAS  Google Scholar 

  90. Doudet DJ, Rosa-Neto P, Munk OL, Ruth TJ, Jivan S, Cumming P (2006) Effect of age on markers for monoaminergic neurons of normal and MPTP-lesioned rhesus monkeys: a multi-tracer PET study. Neuroimage 30:26–35

    Article  PubMed  Google Scholar 

  91. Svenningsson P, Arts J, Gunne L, Andrén PE (2002) Acute and repeated treatment with L-DOPA increase c-jun expression in the 6-hydroxydopamine-lesioned forebrain of rats and common marmosets. Brain Res 955:8–15

    Article  PubMed  CAS  Google Scholar 

  92. Svenningsson P, Gunne L, Andrén PE (2000) L-DOPA produces strong induction of c-fos messenger RNA in dopamine-denervated cortical and striatal areas of the common marmoset. Neuroscience 99:457–468

    Article  PubMed  CAS  Google Scholar 

  93. Caprioli RM, Farmer TB, Gile J (1997) Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal Chem 69:4751–4760

    Article  PubMed  CAS  Google Scholar 

  94. Stoeckli M, Chaurand P, Hallahan DE, Caprioli RM (2001) Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Nat Med 7:493–496

    Article  PubMed  CAS  Google Scholar 

  95. Norris JL, Porter NA, Caprioli RM (2003) Mass spectrometry of intracellular and membrane proteins using cleavable detergents. Anal Chem 75:6642–6647

    Article  PubMed  CAS  Google Scholar 

  96. Norris JL, Porter NA, Caprioli RM (2005) Combination detergent/MALDI matrix: functional cleavable detergents for mass spectrometry. Anal Chem 77:5036–5040

    Article  PubMed  CAS  Google Scholar 

  97. Pierson J, Svenningsson P, Caprioli RM, Andrén PE (2005) Increased levels of ubiquitin in the 6-OHDA-lesioned striatum of rats. J Proteome Res 4:223–226

    Article  PubMed  CAS  Google Scholar 

  98. Sköld K, Svensson M, Nilsson A, et al. (2006) Decreased striatal levels of PEP-19 following MPTP lesion in the mouse. J Proteome Res 5:262–269

    Article  PubMed  CAS  Google Scholar 

  99. Pierson J, Norris JL, Aerni HR, Svenningsson P, Caprioli RM, Andrén PE (2004) Molecular profiling of experimental Parkinson’s disease: direct analysis of peptides and proteins on brain tissue sections by MALDI mass spectrometry. J Proteome Res 3:289–295

    Article  PubMed  CAS  Google Scholar 

  100. Mimnaugh EG, Bonvini P, Neckers L (1999) The measurement of ubiquitin and ubiquitinated proteins. Electrophoresis 20:418–428

    Article  PubMed  CAS  Google Scholar 

  101. Muller S, Schwartz LM (1995) Ubiquitin in homeostasis, development and disease. Bioessays 17:677–684

    Article  PubMed  CAS  Google Scholar 

  102. Andersen JK (2000) What causes the build-up of ubiquitin-containing inclusions in Parkinson’s disease? Mech Ageing Dev 118:15–22

    Article  PubMed  CAS  Google Scholar 

  103. Rohner TC, Staab D, Stoeckli M (2005) MALDI mass spectrometric imaging of biological tissue sections. Mech Ageing Dev 126:177–185

    Article  PubMed  CAS  Google Scholar 

  104. Stoeckli M, Staab D, Staufenbiel M, Wiederhold KH, Signor L (2002) Molecular imaging of amyloid beta peptides in mouse brain sections using mass spectrometry. Anal Biochem 311:33–39

    Article  PubMed  CAS  Google Scholar 

  105. Wagner HN Jr, Burns HD, Dannals RF, et al. (1983) Imaging dopamine receptors in the human brain by positron tomography. Science 221:1264–1266

    Article  PubMed  CAS  Google Scholar 

  106. Bergström M, Grahnén A, Långström B (2003) Positron emission tomography microdosing: a new concept with application in tracer and early clinical drug development. Eur J Clin Pharmacol 59:357–366

    Article  PubMed  Google Scholar 

  107. Court JA, Piggott MA, Lloyd S, et al. (2000) Nicotine binding in human striatum: elevation in schizophrenia and reductions in dementia with Lewy bodies, Parkinson’s disease and Alzheimer’s disease and in relation to neuroleptic medication. Neuroscience 98:79–87

    Article  PubMed  CAS  Google Scholar 

  108. Pimlott SL, Piggott M, Owens J, et al. (2004) Nicotinic acetylcholine receptor distribution in Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease, and vascular dementia: in vitro binding study using 5-[125I]-A-85380. Neuropsychopharmacology 29:108–116

    Article  PubMed  CAS  Google Scholar 

  109. Schmaljohann J, Minnerop M, Karwath P, et al. (2004) Imaging of central nACh receptors with 2-[18F]F-A85380: optimized synthesis and in vitro evaluation in Alzheimer’s disease. Appl Radiat Isot 61:1235–1240

    Article  PubMed  CAS  Google Scholar 

  110. Aerni HR, Cornett DS, Caprioli RM (2006) Automated acoustic matrix deposition for MALDI sample preparation. Anal Chem 78:827–834

    Article  PubMed  CAS  Google Scholar 

  111. Stoeckli M, Farmer TB, Caprioli RM (1999) Automated mass spectrometry imaging with a matrix-assisted laser desorption ionization time-of-flight instrument. J Am Soc Mass Spectrom 10:67–71

    Article  PubMed  CAS  Google Scholar 

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Långström, B., Andrén, P.E., Lindhe, Ö. et al. In Vitro Imaging Techniques in Neurodegenerative Diseases. Mol Imaging Biol 9, 161–175 (2007). https://doi.org/10.1007/s11307-007-0088-1

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