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Technology Insight: imaging amyloid plaques in the living brain with positron emission tomography and MRI

Nature Clinical Practice Neurology volume 1, pages 96–105 (2005)Cite this article

Abstract

Alois Alzheimer first imaged amyloid plaques in 1906 by examining dead tissue under the microscope, but their clinical significance has remained undetermined. Now, nearly a century later, investigators are beginning to image amyloid plaques in living brains using both positron emission tomography and MRI. In this article, we review the studies that report on these recent technical advances, and discuss their potential importance in clarifying the diagnostic and pathogenic relevance of amyloid plaques to Alzheimer's disease.

Key Points

  • Alzheimer's disease (AD) is emerging as one of the most common brain disorders, and considerable progress towards elucidating its molecular biology has been made in the past few years

  • Early studies indicated that insoluble species of amyloid β (Aβ) were most toxic to neurons, but recent studies in transgenic mice indicate that the soluble species of Aβ are the key neurotoxins in AD

  • Postmortem studies have provided a preliminary map of amyloid plaque localization and progression, but the ultimate goal is to image amyloid plaques in living patients

  • Radiolabeled ligands have been developed to enable amyloid plaques to be visualized by positron emission tomography, and this has been successfully accomplished in humans

  • MRI is safer than positron emission tomography, and should also have better spatial resolution; to date, its potential has only been explored in transgenic mice, and numerous technical hurdles need to be overcome before it can be applied to humans

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Figure 1: In vivo imaging promises to clarify the onset and progression of amyloid plaque distribution, as provisionally mapped by postmortem studies.
Figure 2: Positron emission tomography (PET) studies imaging amyloid plaques in vivo.
Figure 3: MRI studies imaging amyloid plaques in vivo.

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References

  1. Alzheimer A (1906) Uber einen eigenartigen schweren erkrankugundgsprozes der Hirnrinde. Neurologisches Centralblatt 23: 1129–1136

    Google Scholar 

  2. Glenner GG and Wong CW (1984) Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 122: 1131–1135

    Article  CAS  Google Scholar 

  3. Selkoe DJ and Podlisny MB (2002) Deciphering the genetic basis of Alzheimer's disease. Annu Rev Genomics Hum Genet 3: 67–99

    Article  CAS  Google Scholar 

  4. Duff K (2001) Transgenic mouse models of Alzheimer's disease: phenotype and mechanisms of pathogenesis. Biochem Soc Symp 67: 195–202

    Article  CAS  Google Scholar 

  5. Mucke L et al. (2000) High-level neuronal expression of Aβ1–42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 20: 4050–4058

    Article  CAS  Google Scholar 

  6. Pearson RC et al. (1985) Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer disease. Proc Natl Acad Sci USA 82: 4531–4534

    Article  CAS  Google Scholar 

  7. Price JL et al. (1991) The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease. Neurobiol Aging 12: 295–312

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Thal DR et al. (2002) Phases of Aβ-deposition in the human brain and its relevance for the development of AD. Neurology 58: 1791–1800

    Article  Google Scholar 

  10. Schonheit B et al. (2004) Spatial and temporal relationships between plaques and tangles in Alzheimer-pathology. Neurobiol Aging 25: 697–711

    Article  Google Scholar 

  11. Shoghi-Jadid K et al. (2002) Localization of neurofibrillary tangles and β-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry 10: 24–35

    Article  Google Scholar 

  12. Klunk WE et al. (2004) Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol 55: 306–319

    Article  CAS  Google Scholar 

  13. Toyama H et al. (2005) PET imaging of brain with the β-amyloid probe, [11C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer's disease. Eur J Nucl Med Mol Imaging 32: 593–600

    Article  CAS  Google Scholar 

  14. Kung MP et al. (2004) Binding of two potential imaging agents targeting amyloid plaques in postmortem brain tissues of patients with Alzheimer's disease. Brain Res 1025: 98–105

    Article  CAS  Google Scholar 

  15. Suemoto T et al. (2004) In vivo labeling of amyloid with BF-108. Neurosci Res 48: 65–74

    Article  CAS  Google Scholar 

  16. Verhoeff NP et al. (2004) In-vivo imaging of Alzheimer disease β-amyloid with [11C]SB-13 PET. Am J Geriatr Psychiatry 12: 584–595

    PubMed  Google Scholar 

  17. Masur DM et al. (1994) Neuropsychological prediction of dementia and the absence of dementia in healthy elderly persons. Neurology 44: 1427–1432

    Article  CAS  Google Scholar 

  18. Jacobs DM et al. (1995) Neuropsychological detection and characterization of preclinical Alzheimer's disease. Neurology 45: 957–962

    Article  CAS  Google Scholar 

  19. Amaral DG and Witter MP (1989) The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31: 571–591

    Article  CAS  Google Scholar 

  20. Zhao X et al. (2001) Transcriptional profiling reveals strict boundaries between hippocampal subregions. J Comp Neurol 441: 187–196

    Article  CAS  Google Scholar 

  21. Small SA (2001) Age-related memory decline; current concepts and future directions. Arch Neurol 58: 360–364

    Article  CAS  Google Scholar 

  22. Small SA (2003) Imaging Alzheimer's disease. Curr Neurol Neurosci Rep 3: 385–392

    Article  Google Scholar 

  23. Arnold SE et al. (1991) The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. Cereb Cortex 1: 103–116

    Article  CAS  Google Scholar 

  24. Giannakopoulos P et al. (2003) Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology 60: 1495–1500

    Article  CAS  Google Scholar 

  25. Gyure KA et al. (2001) Intraneuronal Aβ-amyloid precedes development of amyloid plaques in Down syndrome. Arch Pathol Lab Med 125: 489–492

    CAS  PubMed  Google Scholar 

  26. Lue LF et al. (1999) Soluble amyloid β peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am J Pathol 155: 853–862

    Article  CAS  Google Scholar 

  27. Takahashi RH et al. (2002) Intraneuronal Alzheimer Aβ42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am J Pathol 161: 1869–1879

    Article  CAS  Google Scholar 

  28. Lee SP et al. (2004) Visualization of β-amyloid plaques in a transgenic mouse model of Alzheimer's disease using MR microscopy without contrast reagents. Magn Reson Med 52: 538–544

    Article  Google Scholar 

  29. Benveniste H et al. (1999) Detection of neuritic plaques in Alzheimer's disease by magnetic resonance microscopy. Proc Natl Acad Sci USA 96: 14079–14084

    Article  CAS  Google Scholar 

  30. Higuchi M et al. (2005) 19F and 1H MRI detection of amyloid β plaques in vivo. Nat Neurosci 8: 527–533

    Article  CAS  Google Scholar 

  31. Helpern JA et al. (2004) MRI assessment of neuropathology in a transgenic mouse model of Alzheimer's disease. Magn Reson Med 51: 794–798

    Article  Google Scholar 

  32. Jack CR Jr et al. (2004) In vivo visualization of Alzheimer's amyloid plaques by magnetic resonance imaging in transgenic mice without a contrast agent. Magn Reson Med 52: 1263–1271

    Article  Google Scholar 

  33. Vanhoutte G et al. (2005) Noninvasive in vivo MRI detection of neuritic plaques associated with iron in APP[V717I] transgenic mice, a model for Alzheimer's disease. Magn Reson Med 53: 607–613

    Article  CAS  Google Scholar 

  34. Wadghiri YZ et al. (2003) Detection of Alzheimer's amyloid in transgenic mice using magnetic resonance microimaging. Magn Reson Med 50: 293–302

    Article  CAS  Google Scholar 

  35. Falangola MF et al. (2005) Histological co-localization of iron in Aβ plaques of PS/APP transgenic mice. Neurochem Res 30: 201–205

    Article  CAS  Google Scholar 

  36. Skovronsky DM et al. (2000) In vivo detection of amyloid plaques in a mouse model of Alzheimer's disease. Proc Natl Acad Sci USA 97: 7609–7614

    Article  CAS  Google Scholar 

  37. Sossi V and Ruth TJ (2005) Micropet imaging: in vivo biochemistry in small animals. J Neural Transm 112: 319–330

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by NIH grants AG08702 and AG025161.

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Authors and Affiliations

  1. Columbia University Medical Center and a member of the Columbia Medical School Class of 2006,

    Dan E Huddleston & Scott A Small

  2. Columbia University Medical Center, New York, NY, USA

    Dan E Huddleston & Scott A Small

Authors
  1. Dan E Huddleston
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  2. Scott A Small
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Correspondence to Scott A Small.

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The authors declare no competing financial interests.

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Huddleston, D., Small, S. Technology Insight: imaging amyloid plaques in the living brain with positron emission tomography and MRI. Nat Rev Neurol 1, 96–105 (2005). https://doi.org/10.1038/ncpneuro0046

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