Current Neurology and Neuroscience Reports

, Volume 9, Issue 5, pp 345–352

Update on amyloid imaging: From healthy aging to Alzheimer’s disease

Article

Abstract

We report on the current state of in vivo amyloid imaging. Although this technique is less than a decade old, a wealth of information is emerging as the initial clinical studies are being reported. Imaging of patients with Alzheimer’s disease has allowed quantitative exploration of the natural history of amyloid deposition and its relationship to neurodegeneration. Amyloid imaging also shows significant promise in the differential diagnosis of mild cognitive impairment or atypical dementias. However, amyloid detection may be of greatest utility in healthy elderly persons; consistent with prior autopsy studies, a significant proportion of asymptomatic individuals display increased levels of amyloid by in vivo imaging. Understanding the relationship between this pathology and future cognitive status has significant implications for the application of disease-modifying medications in the “preclinical” phase of disease. Given the considerable clinical experience compared with other tracers, this review focuses on the literature involving Pittsburgh compound B positron emission tomography.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Small GW, Kepe V, Ercoli LM, et al.: PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med 2006, 355:2652–2663.PubMedCrossRefGoogle Scholar
  2. 2.
    Verhoeff NP, Wilson AA, Takeshita S, et al.: In-vivo imaging of Alzheimer disease beta-amyloid with [11C]SB-13 PET. Am J Geriatr Psychiatry 2004, 12:584–595.PubMedGoogle Scholar
  3. 3.
    Klunk WE, Engler H, Nordberg A, et al.: Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 2004, 55:306–319.PubMedCrossRefGoogle Scholar
  4. 4.
    Mueller SG, Weiner MW, Thal LJ, et al.: The Alzheimer’s disease neuroimaging initiative. Neuroimaging Clin N Am 2005, 15:869–877, xi–xii.PubMedCrossRefGoogle Scholar
  5. 5.
    Klunk WE, Lopresti BJ, Ikonomovic MD, et al.: Binding of the positron emission tomography tracer Pittsburgh compound-B reflects the amount of amyloid-beta in Alzheimer’s disease brain but not in transgenic mouse brain. J Neurosci 2005, 25:10598–10606.PubMedCrossRefGoogle Scholar
  6. 6.
    Klunk WE, Wang Y, Huang GF, et al.: The binding of 2-(4′-methylaminophenyl)benzothiazole to postmortem brain homogenates is dominated by the amyloid component. J Neurosci 2003, 23:2086–2092.PubMedGoogle Scholar
  7. 7.
    Thal DR, Rub U, Orantes M, Braak H: Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 2002, 58:1791–1800.PubMedGoogle Scholar
  8. 8.
    Fagan AM, Mintun MA, Mach RH, et al.: Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann Neurol 2006, 59:512–519.PubMedCrossRefGoogle Scholar
  9. 9.
    Ikonomovic MD, Klunk WE, Abrahamson EE, et al.: Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease. Brain 2008, 131:1630–1645.PubMedCrossRefGoogle Scholar
  10. 10.
    Bacskai BJ, Frosch MP, Freeman SH, et al.: Molecular imaging with Pittsburgh compound B confirmed at autopsy: a case report. Arch Neurol 2007, 64:431–434.PubMedCrossRefGoogle Scholar
  11. 11.
    Leinonen V, Alafuzoff I, Aalto S, et al.: 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 2008, 65:1304–1309.PubMedCrossRefGoogle Scholar
  12. 12.
    Klunk WE: Biopsy support for the validity of Pittsburgh compound B positron emission tomography with a twist. Arch Neurol 2008, 65:1281–1283.PubMedCrossRefGoogle Scholar
  13. 13.
    Braak H, Braak E: Neuropathological staging of Alzheimer-related changes. Acta Neuropathol 1991, 82:239–259.PubMedCrossRefGoogle Scholar
  14. 14.
    Kemppainen NM, Aalto S, Wilson IA, et al.: PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology 2007, 68:1603–1606.PubMedCrossRefGoogle Scholar
  15. 15.
    Rowe CC, Ng S, Ackermann U, et al.: Imaging beta-amyloid burden in aging and dementia. Neurology 2007, 68:1718–1725.PubMedCrossRefGoogle Scholar
  16. 16.
    Edison P, Archer HA, Hinz R, et al.: Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study. Neurology 2007, 68:501–508.PubMedCrossRefGoogle Scholar
  17. 17.
    Jack CR Jr, Lowe VJ, Weigand SD, et al.: Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer’s disease: implications for sequence of pathological events in Alzheimer’s disease. Brain 2009, 132(Pt 5):1355–1365.PubMedCrossRefGoogle Scholar
  18. 18.
    Dubois B, Feldman HH, Jacova C, et al.: Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007, 6:734–746.PubMedCrossRefGoogle Scholar
  19. 19.
    Engler H, Forsberg A, Almkvist O, et al.: Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain 2006, 129:2856–2866.PubMedCrossRefGoogle Scholar
  20. 20.
    Klunk WE, Mathis CA, Price JC, et al.: Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease [commentary]. Brain 2006, 129:2805–2807.PubMedCrossRefGoogle Scholar
  21. 21.
    Terry RD, Masliah E, Salmon DP, et al.: Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991, 30:572–580.PubMedCrossRefGoogle Scholar
  22. 22.
    DeKosky ST, Scheff SW: Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol 1990, 27:457–464.PubMedCrossRefGoogle Scholar
  23. 23.
    Stern Y, Gurland B, Tatemichi TK, et al.: Influence of education and occupation on the incidence of Alzheimer’s disease. JAMA 1994, 271:1004–1010.PubMedCrossRefGoogle Scholar
  24. 24.
    Roe CM, Xiong C, Miller JP, Morris JC: Education and Alzheimer disease without dementia: support for the cognitive reserve hypothesis. Neurology 2007, 68:223–228.PubMedCrossRefGoogle Scholar
  25. 25.
    Bennett DA, Schneider JA, Wilson RS, et al.: Education modifies the association of amyloid but not tangles with cognitive function. Neurology 2005, 65:953–955.PubMedCrossRefGoogle Scholar
  26. 26.
    Kemppainen NM, Aalto S, Karrasch M, et al.: Cognitive reserve hypothesis: Pittsburgh compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer’s disease. Ann Neurol 2008, 63:112–118.PubMedCrossRefGoogle Scholar
  27. 27.
    Nelissen N, Vandenbulcke M, Fannes K, et al.: Abeta amyloid deposition in the language system and how the brain responds. Brain 2007, 130:2055–2069.PubMedCrossRefGoogle Scholar
  28. 28.
    Johansson A, Savitcheva I, Forsberg A, et al.: [(11)C]-PIB imaging in patients with Parkinson’s disease: preliminary results. Parkinsonism Relat Disord 2008, 14:345–347.PubMedCrossRefGoogle Scholar
  29. 29.
    Maetzler W, Reimold M, Liepelt I, et al.: [11C]PIB binding in Parkinson’s disease dementia. Neuroimage 2008, 39:1027–1033.PubMedCrossRefGoogle Scholar
  30. 30.
    McKeith I, Mintzer J, Aarsland D, et al.: Dementia with Lewy bodies. Lancet Neurol 2004, 3:19–28.PubMedCrossRefGoogle Scholar
  31. 31.
    Alladi S, Xuereb J, Bak T, et al.: Focal cortical presentations of Alzheimer’s disease. Brain 2007, 130:2636–2645.PubMedCrossRefGoogle Scholar
  32. 32.
    Rabinovici GD, Furst AJ, O’Neil JP, et al.: 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology 2007, 68:1205–1212.PubMedCrossRefGoogle Scholar
  33. 33.
    Rabinovici GD, Jagust WJ, Furst AJ, et al.: Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol 2008, 64:388–401.PubMedCrossRefGoogle Scholar
  34. 34.
    Mesulam M, Wicklund A, Johnson N, et al.: Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Ann Neurol 2008, 63:709–719.PubMedCrossRefGoogle Scholar
  35. 35.
    Petersen RC: Mild cognitive impairment as a diagnostic entity. J Intern Med 2004, 256:183–194.PubMedCrossRefGoogle Scholar
  36. 36.
    Visser PJ, Kester A, Jolles J, Verhey F: Ten-year risk of dementia in subjects with mild cognitive impairment. Neurology 2006, 67:1201–1207.PubMedCrossRefGoogle Scholar
  37. 37.
    Jicha GA, Parisi JE, Dickson DW, et al.: Neuropathologic outcome of mild cognitive impairment following progression to clinical dementia. Arch Neurol 2006, 63:674–681.PubMedCrossRefGoogle Scholar
  38. 38.
    Larrieu S, Letenneur L, Orgogozo JM, et al.: Incidence and outcome of mild cognitive impairment in a population-based prospective cohort. Neurology 2002, 59:1594–1599.PubMedGoogle Scholar
  39. 39.
    Fleisher AS, Sowell BB, Taylor C, et al.: Clinical predictors of progression to Alzheimer disease in amnestic mild cognitive impairment. Neurology 2007, 68:1588–1595.PubMedCrossRefGoogle Scholar
  40. 40.
    Jack CR, Petersen RC, Xu YC, et al.: Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology 1999, 52:1397–1403.PubMedGoogle Scholar
  41. 41.
    Hansson O, Zetterberg H, Buchhave P, et al.: Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 2006, 5:228–234.PubMedCrossRefGoogle Scholar
  42. 42.
    Drzezga A, Grimmer T, Riemenschneider M, et al.: Prediction of individual clinical outcome in MCI by means of genetic assessment and (18)F-FDG PET. J Nucl Med 2005, 46:1625–1632.PubMedGoogle Scholar
  43. 43.
    Forsberg A, Engler H, Almkvist O, et al.: PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging 2008, 29:1456–1465.PubMedCrossRefGoogle Scholar
  44. 44.
    Pike KE, Savage G, Villemagne VL, et al.: Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer’s disease. Brain 2007, 130:2837–2844.PubMedCrossRefGoogle Scholar
  45. 45.
    Jack CR Jr, Lowe VJ, Senjem ML, et al.: 11C PiB and structural MRI provide complementary information in imaging of Alzheimer’s disease and amnestic mild cognitive impairment. Brain 2008, 131:665–680.PubMedCrossRefGoogle Scholar
  46. 46.
    Wolk DA, Price JC, Saxton JA, et al.: Amyloid imaging in mild cognitive impairment subtypes. Ann Neurol 2009, 65:557–568.PubMedCrossRefGoogle Scholar
  47. 47.
    Koivunen J, Pirttila T, Kemppainen N, et al.: PET amyloid ligand [11C]PIB uptake and cerebrospinal fluid beta-amyloid in mild cognitive impairment. Dement Geriatr Cogn Disord 2008, 26:378–383.PubMedCrossRefGoogle Scholar
  48. 48.
    Price JL, Morris JC: Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol 1999, 45:358–368.PubMedCrossRefGoogle Scholar
  49. 49.
    Aizenstein HJ, Nebes RD, Saxton JA, et al.: Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol 2008, 65:1509–1517.PubMedCrossRefGoogle Scholar
  50. 50.
    Villemagne VL, Pike KE, Darby D, et al.: Abeta deposits in older non-demented individuals with cognitive decline are indicative of preclinical Alzheimer’s disease. Neuropsychologia 2008, 46:1688–1697.PubMedCrossRefGoogle Scholar
  51. 51.
    Dickerson BC, Bakkour A, Salat DH, et al.: The cortical signature of Alzheimer’s disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cereb Cortex 2009, 19:497–510.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group, LLC 2009

Authors and Affiliations

  1. 1.Department of Neurology, Penn Memory CenterUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations