The use of PET in Alzheimer disease


In Alzheimer disease (AD), which is the most common cause of dementia, the underlying disease pathology most probably precedes the onset of cognitive symptoms by many years. Thus, efforts are underway to find early diagnostic markers as well as disease-modifying treatments for this disorder. PET enables various brain systems to be monitored in living individuals. In patients with AD, PET can be used to investigate changes in cerebral glucose metabolism, various neurotransmitter systems, neuroinflammation, and the protein aggregates that are characteristic of the disease, notably the amyloid deposits. These investigations are helping to further our understanding of the complex pathophysiological mechanisms that underlie AD, as well as aiding the early and differential diagnosis of the disease in the clinic. In the future, PET studies will also be useful for identifying new therapeutic targets and monitoring treatment outcomes. Amyloid imaging could be useful as early diagnostic marker of AD and for selecting patients for anti-amyloid-β therapy, while cerebral glucose metabolism could be a suitable PET marker for monitoring disease progression. For the near future, multitracer PET studies are unlikely to be used routinely in the clinic for AD, being both burdensome and expensive; however, such studies are very informative in a research context.

Key Points

  • PET studies facilitate the clinical differentiation between Alzheimer disease (AD) and other types of dementia

  • Monitoring cerebral glucose metabolism or amyloid deposition by PET could provide diagnostic accuracy in early cognitive impairment

  • PET amyloid imaging permits the early detection of patients with amnestic mild cognitive impairment—individuals who have a high risk of developing AD

  • The glucose analog 2-[18F]-fluoro-2-deoxy-D-glucose can be used in PET studies to monitor the clinical progression of AD

  • PET amyloid imaging has the potential to be used for selecting appropriate patients for future anti-amyloid-β therapies

  • Multitracer PET studies further our understanding of the underlying pathological disease processes in AD and the relationship between such pathology and the cognitive impairment exhibited by patients

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Figure 1: A multitracer PET study in Alzheimer disease.
Figure 2: Chemical structures of amyloid PET tracers.
Figure 3: Amyloid imaging in AD.
Figure 4: Fusion images from coregistered PET and MRI scans.
Figure 5: Regional changes in amyloid load and cerebral glucose metabolism.
Figure 6: Time course of events in AD.


  1. 1

    Brookmeyer, R., Johnson, E., Ziegler-Graha, K. & Arrighi, H. M. Forecasting the global burden of Alzheimer's disease. Alzheimers Dement. 3, 186–191 (2007).

    PubMed  Google Scholar 

  2. 2

    Thal, D. R., Rub, U., Orantes, M. & Braak, H. Phases of Aβ-deposition in the human brain and its relevance for the development of AD. Neurology 58, 1791–1800 (2002).

    PubMed  PubMed Central  Google Scholar 

  3. 3

    Mattson, M. P. Pathways towards and away from Alzheimer's disease. Nature 430, 631–639 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4

    Dubois, B. et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria. Lancet Neurol. 6, 734–746 (2007).

    Google Scholar 

  5. 5

    Herholz, K., Carter, S. F. & Jones, M. Positron emission tomography imaging in dementia. Br. J. Radiol. 80 (Spec. No. 2), S160–S167 (2007).

    PubMed  Google Scholar 

  6. 6

    Small, G. W. et al. Current and future uses of neuroimaging for cognitively impaired patients. Lancet Neurol. 7, 161–172 (2008).

    PubMed  PubMed Central  Google Scholar 

  7. 7

    Mosconi, L. et al. FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer's disease. Eur. J. Nucl. Med. Mol. Imaging 36, 811–822 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8

    Mosconi, L. Brain glucose metabolism in the early and specific diagnosis of Alzheimer's disease. FDG-PET studies in MCI and AD. Eur. J. Nucl. Med. Mol. Imaging 32, 486–510 (2005).

    CAS  PubMed  Google Scholar 

  9. 9

    Engler, H. et al. Two-year follow-up of amyloid deposition in patients with Alzheimer's disease. Brain 129, 2856–2866 (2006).

    PubMed  Google Scholar 

  10. 10

    Jagust, W., Reed, B., Mungas, D., Ellis, W. & Decarli, C. What does fluorodeoxyglucose PET imaging add to a clinical diagnosis of dementia? Neurology 69, 871–877 (2007).

    CAS  PubMed  Google Scholar 

  11. 11

    Drzezga, A. et al. Prediction of individual clinical outcome in MCI by means of genetic assessment and 18F-FDG PET. J. Nucl. Med. 46, 1625–1632 (2005).

    CAS  PubMed  Google Scholar 

  12. 12

    Drzezga, A. et al. Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study. Eur. J. Nucl. Med. Mol. Imaging 30, 1104–1113 (2003).

    PubMed  Google Scholar 

  13. 13

    Mosconi, L. et al. Early detection of Alzheimer's disease using neuroimaging. Exp. Gerontol. 42, 129–138 (2007).

    PubMed  Google Scholar 

  14. 14

    Minoshima, S., Foster, N. L. & Kuhl, D. E. Posterior cingulate cortex in Alzheimer's disease. Lancet 344, 895 (1994).

    CAS  PubMed  Google Scholar 

  15. 15

    Minoshima, S. et al. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann. Neurol. 42, 85–94 (1997).

    CAS  PubMed  Google Scholar 

  16. 16

    Schöll, M. et al. Glucose metabolism and PIB binding in carriers of a His163Tyr presenilin 1 mutation. Neurobiol. Aging doi:10.1016/j.neurobiolaging.2009.08.016.

    PubMed  Google Scholar 

  17. 17

    Reiman, E. M. et al. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proc. Natl Acad. Sci. USA 101, 284–289 (2004).

    CAS  PubMed  Google Scholar 

  18. 18

    Small, G. W. et al. Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA 273, 942–947 (1995).

    CAS  PubMed  Google Scholar 

  19. 19

    Reiman, E. M. et al. Declining brain activity in cognitively normal apolipoprotein E ε4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease. Proc. Natl Acad. Sci. USA 98, 3334–3339 (2001).

    CAS  PubMed  Google Scholar 

  20. 20

    Reiman, E. M. et al. Preclinical evidence of Alzheimer's disease in persons homozygous for the ε4 allele for apolipoprotein E. N. Engl. J. Med. 334, 752–758 (1996).

    CAS  PubMed  Google Scholar 

  21. 21

    Pedersen, N. L., Gatz, M., Berg, S. & Johansson, B. How heritable is Alzheimer's disease late in life? Findings from Swedish twins. Ann. Neurol. 55, 180–185 (2004).

    PubMed  Google Scholar 

  22. 22

    Järvenpää, T. et al. Regional cerebral glucose metabolism in monozygotic twins discordant for Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 16, 245–252 (2003).

    PubMed  Google Scholar 

  23. 23

    Virta, J. J. et al. Voxel-based analysis of cerebral glucose metabolism in mono- and dizygotic twins discordant for Alzheimer disease. J. Neurol. Neurosurg. Psychiatry 80, 259–266 (2009).

    CAS  PubMed  Google Scholar 

  24. 24

    Mosconi, L. et al. Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism. Proc. Natl Acad. Sci. USA 104, 19067–19072 (2007).

    CAS  PubMed  Google Scholar 

  25. 25

    Braak, H., de Vos, R. A., Jansen, E. N., Bratzke, H. & Braak, E. Neuropathological hallmarks of Alzheimer's and Parkinson's diseases. Prog. Brain Res. 117, 267–285 (1998).

    CAS  PubMed  Google Scholar 

  26. 26

    Perry, E. K., Perry, R. H., Blessed, G. & Tomlinson, B. E. Changes in brain cholinesterases in senile dementia of Alzheimer type. Neuropathol. Appl. Neurobiol. 4, 273–277 (1978).

    CAS  PubMed  Google Scholar 

  27. 27

    Rinne, J. O. et al. Brain acetylcholinesterase activity in mild cognitive impairment and early Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 74, 113–115 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Herholz, K., Weisenbach, S., Kalbe, E., Diederich, N. J. & Heiss, W. D. Cerebral acetylcholine esterase activity in mild cognitive impairment. Neuroreport 16, 1431–1434 (2005).

    CAS  PubMed  Google Scholar 

  29. 29

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

    CAS  PubMed  Google Scholar 

  30. 30

    Kadir, A., Almkvist, O., Wall, A., Långström, B. & Nordberg, A. PET imaging of cortical 11C-nicotine binding correlates with the cognitive function of attention in Alzheimer's disease. Psychopharmacology (Berl.) 188, 509–520 (2006).

    CAS  Google Scholar 

  31. 31

    Horti, A. G., Gao, Y., Kuwabara, H. & Dannals, R. F. Development of radioligands with optimized imaging properties for quantification of nicotinic acetylcholine receptors by positron emission tomography. Life Sci. doi:10.1016/j.lfs.2009.02.029.

    CAS  PubMed  Google Scholar 

  32. 32

    Sabri, O., Kendziorra, K., Wolf, H., Gertz, H. J. & Brust, P. Acetylcholine receptors in dementia and mild cognitive impairment. Eur. J. Nucl. Med. Mol. Imaging 35 (Suppl. 1), S30–S45 (2008).

    CAS  PubMed  Google Scholar 

  33. 33

    Pomper, M. G. et al. Synthesis and biodistribution of radiolabeled α7 nicotinic acetylcholine receptor ligands. J. Nucl. Med. 46, 326–334 (2005).

    CAS  PubMed  Google Scholar 

  34. 34

    Toyohara, J. et al. Preclinical and the first clinical studies on [11C]CHIBA-1001 for mapping α7 nicotinic receptors by positron emission tomography. Ann. Nucl. Med. 23, 301–309 (2009).

    CAS  PubMed  Google Scholar 

  35. 35

    Zubieta, J. K. et al. Assessment of muscarinic receptor concentrations in aging and Alzheimer disease with [11C]NMPB and PET. Synapse 39, 275–287 (2001).

    CAS  PubMed  Google Scholar 

  36. 36

    Cohen, R. M. et al. Higher in vivo muscarinic-2 receptor distribution volumes in aging subjects with an apolipoprotein E-ε4 allele. Synapse 49, 150–156 (2003).

    CAS  PubMed  Google Scholar 

  37. 37

    Reinikainen, K. J., Soininen, H. & Riekkinen, P. J. Neurotransmitter changes in Alzheimer's disease: implications to diagnostics and therapy. J. Neurosci. Res. 27, 576–586 (1990).

    CAS  PubMed  Google Scholar 

  38. 38

    Rinne, J. O., Sahlberg, N., Ruottinen, H., Nagren, K. & Lehikoinen, P. Striatal uptake of the dopamine reuptake ligand [11C]β-CFT is reduced in Alzheimer's disease assessed by positron emission tomography. Neurology 50, 152–156 (1998).

    CAS  PubMed  Google Scholar 

  39. 39

    Walker, Z. et al. Differentiation of dementia with Lewy bodies from Alzheimer's disease using a dopaminergic presynaptic ligand. J. Neurol. Neurosurg. Psychiatry 73, 134–140 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40

    McKeith, I. et al. Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol. 6, 305–313 (2007).

    PubMed  Google Scholar 

  41. 41

    Walker, Z. et al. Dementia with Lewy bodies: a comparison of clinical diagnosis, FP-CIT single photon emission computed tomography imaging and autopsy. J. Neurol. Neurosurg. Psychiatry 78, 1176–1181 (2007).

    PubMed  PubMed Central  Google Scholar 

  42. 42

    Kemppainen, N., Ruottinen, H., Någren, K. & Rinne, J. O. PET shows that striatal dopamine D1 and D2 receptors are differentially affected in AD. Neurology 55, 205–209 (2000).

    CAS  PubMed  Google Scholar 

  43. 43

    Tanaka, Y. et al. Decreased striatal D2 receptor density associated with severe behavioral abnormality in Alzheimer's disease. Ann. Nucl. Med. 17, 567–573 (2003).

    PubMed  Google Scholar 

  44. 44

    Kemppainen, N. et al. Hippocampal dopamine D2 receptors correlate with memory functions in Alzheimer's disease. Eur. J. Neurosci. 18, 149–154 (2003).

    CAS  PubMed  Google Scholar 

  45. 45

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

    CAS  PubMed  Google Scholar 

  46. 46

    Kepe, V. et al. Serotonin 1A receptors in the living brain of Alzheimer's disease patients. Proc. Natl Acad. Sci. USA 103, 702–707 (2006).

    CAS  PubMed  Google Scholar 

  47. 47

    Meltzer, C. C. et al. PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders. Am. J. Psychiatry 156, 1871–1878 (1999).

    CAS  PubMed  Google Scholar 

  48. 48

    Jagust, W. Mapping brain β-amyloid. Curr. Opin. Neurol. 22, 356–361 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49

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

    CAS  Google Scholar 

  50. 50

    Klunk, W. E. et al. 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 (2005).

    CAS  PubMed  Google Scholar 

  51. 51

    Ikonomovic, M. D. et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain 131, 1630–1645 (2008).

    PubMed  PubMed Central  Google Scholar 

  52. 52

    Leinonen, V. et al. Assessment of β-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 (2008).

    PubMed  Google Scholar 

  53. 53

    Svedberg, M. M. et al. [11C]PIB-amyloid binding and levels of Aβ40 and Aβ42 in postmortem brain tissue from Alzheimer patients. Neurochem. Int. 54, 347–357 (2009).

    CAS  PubMed  Google Scholar 

  54. 54

    Archer, H. A. et al. Amyloid load and cerebral atrophy in Alzheimer's disease: an 11C-PIB positron emission tomography study. Ann. Neurol. 60, 145–147 (2006).

    PubMed  Google Scholar 

  55. 55

    Kemppainen, N. M. et al. Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease. Neurology 67, 1575–1580 (2006).

    CAS  PubMed  Google Scholar 

  56. 56

    Mintun, M. A. et al. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology 67, 446–452 (2006).

    CAS  PubMed  Google Scholar 

  57. 57

    Price, J. C. et al. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B. J. Cereb. Blood Flow Metab. 25, 1528–1547 (2005).

    CAS  PubMed  Google Scholar 

  58. 58

    Rowe, C. C. et al. Imaging β-amyloid burden in aging and dementia. Neurology 68, 1718–1725 (2007).

    CAS  PubMed  Google Scholar 

  59. 59

    Forsberg, A. et al. PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol. Aging 29, 1456–1465 (2008).

    CAS  PubMed  Google Scholar 

  60. 60

    Jack, C. R. Jr 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 132, 1355–1365 (2009).

    PubMed  PubMed Central  Google Scholar 

  61. 61

    Kemppainen, N. M. et al. PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology 68, 1603–1606 (2007).

    CAS  PubMed  Google Scholar 

  62. 62

    Pike, K. E. et al. β-Amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. Brain 130, 2837–2844 (2007).

    PubMed  Google Scholar 

  63. 63

    Okello, A. et al. Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB PET study. Neurology 73, 754–760 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64

    Wolk, D. A. et al. Amyloid imaging in mild cognitive impairment subtypes. Ann. Neurol. 65, 557–568 (2009).

    PubMed  PubMed Central  Google Scholar 

  65. 65

    Lowe, V. J. et al. Comparison of 18F-FDG and PiB PET in cognitive impairment. J. Nucl. Med. 50, 878–886 (2009).

    PubMed  PubMed Central  Google Scholar 

  66. 66

    Forsberg, A. et al. High PIB retention in Alzheimer's disease is an early event with complex relationship with CSF biomarkers and functional parameters. Curr. Alzheimer Res. doi:10.2174/1567210198607192050.

  67. 67

    Fagan, A. M. et al. Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Aβ42 in humans. Ann. Neurol. 59, 512–519 (2006).

    CAS  PubMed  Google Scholar 

  68. 68

    Koivunen, J. et al. PET amyloid ligand [11C]PIB uptake and cerebrospinal fluid beta-amyloid in mild cognitive impairment. Dement. Geriatr. Cogn. Disord. 26, 378–383 (2008).

    CAS  PubMed  Google Scholar 

  69. 69

    Edison, P. et al. Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study. Neurology 68, 501–508 (2007).

    CAS  PubMed  Google Scholar 

  70. 70

    Landau, S. M. et al. Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI. Neurobiol. Aging doi:10.1016/j.neurobiolaging.2009.07.002.

    PubMed  Google Scholar 

  71. 71

    Grimmer, T. et al. Clinical severity of Alzheimer's disease is associated with PIB uptake in PET. Neurobiol. Aging 30, 1902–1909 (2008).

    PubMed  Google Scholar 

  72. 72

    Villemagne, V. L. et al. Aβ deposits in older non-demented individuals with cognitive decline are indicative of preclinical Alzheimer's disease. Neuropsychologia 46, 1688–1697 (2008).

    CAS  PubMed  Google Scholar 

  73. 73

    Drzezga, A. et al. Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer disease. Neurology 72, 1487–1494 (2009).

    CAS  PubMed  Google Scholar 

  74. 74

    Reiman, E. M. et al. Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease. Proc. Natl Acad. Sci. USA 106, 6820–6825 (2009).

    CAS  PubMed  Google Scholar 

  75. 75

    Scheinin, N. M. et al. Follow-up of [11C]PIB uptake and brain volume in patients with Alzheimer disease and controls. Neurology 73, 1186–1192 (2009).

    CAS  PubMed  Google Scholar 

  76. 76

    Edison, P. et al. Amyloid load in Parkinson's disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography. J. Neurol. Neurosurg. Psychiatry 79, 1331–1338 (2008).

    CAS  PubMed  Google Scholar 

  77. 77

    Johansson, A. et al. [11C]-PIB imaging in patients with Parkinson's disease: preliminary results. Parkinsonism Relat. Disord. 14, 345–347 (2008).

    CAS  PubMed  Google Scholar 

  78. 78

    Maetzler, W. et al. [11C]PIB binding in Parkinson's disease dementia. Neuroimage 39, 1027–1033 (2008).

    PubMed  Google Scholar 

  79. 79

    Drzezga, A. et al. Imaging of amyloid plaques and cerebral glucose metabolism in semantic dementia and Alzheimer's disease. Neuroimage 39, 619–633 (2008).

    PubMed  Google Scholar 

  80. 80

    Engler, H. et al. In vivo amyloid imaging with PET in frontotemporal dementia. Eur. J. Nucl. Med. Mol. Imaging 35, 100–106 (2008).

    PubMed  Google Scholar 

  81. 81

    Gomperts, S. N. et al. Imaging amyloid deposition in Lewy body diseases. Neurology 71, 903–910 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82

    Johnson, K. A. et al. Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Ann. Neurol. 62, 229–234 (2007).

    PubMed  Google Scholar 

  83. 83

    Aizenstein, H. J. et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch. Neurol. 65, 1509–1517 (2008).

    PubMed  PubMed Central  Google Scholar 

  84. 84

    Small, G. W. et al. PET of brain amyloid and tau in mild cognitive impairment. N. Engl. J. Med. 355, 2652–2663 (2006).

    CAS  PubMed  Google Scholar 

  85. 85

    Waragai, M. et al. Comparison study of amyloid PET and voxel-based morphometry analysis in mild cognitive impairment and Alzheimer's disease. J. Neurol. Sci. 285, 100–108 (2009).

    PubMed  Google Scholar 

  86. 86

    Rowe, C. C. et al. Imaging of amyloid β in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism. Lancet Neurol. 7, 129–135 (2008).

    CAS  PubMed  Google Scholar 

  87. 87

    Tolboom, N. et al. Detection of Alzheimer pathology in vivo using both 11C-PIB and 18F-FDDNP PET. J. Nucl. Med. 50, 191–197 (2009).

    PubMed  Google Scholar 

  88. 88

    Thompson, P. W. et al. Interaction of the amyloid imaging tracer FDDNP with hallmark Alzheimer's disease pathologies. J. Neurochem. 109, 623–630 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. 89

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

    PubMed  Google Scholar 

  90. 90

    Walsh, D. M. & Selkoe, D. J. Aβ oligomers—a decade of discovery. J. Neurochem. 101, 1172–1184 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. 91

    Cagnin, A. et al. In-vivo measurement of activated microglia in dementia. Lancet 358, 461–467 (2001).

    CAS  Google Scholar 

  92. 92

    Okello, A. et al. Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology 72, 56–62 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93

    Wiley, C. A. et al. Carbon 11-labeled Pittsburgh Compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease. Arch. Neurol. 66, 60–67 (2009).

    PubMed  PubMed Central  Google Scholar 

  94. 94

    Hirsch-Reinshagen, V., Burgess, B. L. & Wellington, C. L. Why lipids are important for Alzheimer disease? Mol. Cell Biochem. 326, 121–129 (2009).

    CAS  PubMed  Google Scholar 

  95. 95

    Kadir, A. et al. PET imaging of the in vivo brain acetylcholinesterase activity and nicotine binding in galantamine-treated patients with AD. Neurobiol. Aging 29, 1204–1217 (2008).

    CAS  PubMed  Google Scholar 

  96. 96

    Bohnen, N. I. et al. Degree of inhibition of cortical acetylcholinesterase activity and cognitive effects by donepezil treatment in Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 76, 315–319 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. 97

    Kuhl, D. E. et al. Limited donepezil inhibition of acetylcholinesterase measured with positron emission tomography in living Alzheimer cerebral cortex. Ann. Neurol. 48, 391–395 (2000).

    CAS  PubMed  Google Scholar 

  98. 98

    Kaasinen, V. et al. Regional effects of donepezil and rivastigmine on cortical acetylcholinesterase activity in Alzheimer's disease. J. Clin. Psychopharmacol. 22, 615–620 (2002).

    CAS  PubMed  Google Scholar 

  99. 99

    Shinotoh, H. et al. Effect of donepezil on brain acetylcholinesterase activity in patients with AD measured by PET. Neurology 56, 408–410 (2001).

    CAS  PubMed  Google Scholar 

  100. 100

    Kadir, A. et al. Changes in brain 11C-nicotine binding sites in patients with mild Alzheimer's disease following rivastigmine treatment as assessed by PET. Psychopharmacology (Berl.) 191, 1005–1014 (2007).

    CAS  Google Scholar 

  101. 101

    Ellis, J. R. et al. Galantamine-induced improvements in cognitive function are not related to alterations in α4β2 nicotinic receptors in early Alzheimer's disease as measured in vivo by 2-[18F]fluoro-A-85380 PET. Psychopharmacology (Berl.) 202, 79–91 (2009).

    CAS  Google Scholar 

  102. 102

    Diehl-Schmid, J. et al. Longitudinal changes of cerebral glucose metabolism in semantic dementia. Dement. Geriatr. Cogn. Disord. 22, 346–351 (2006).

    CAS  PubMed  Google Scholar 

  103. 103

    Diehl-Schmid, J. et al. Decline of cerebral glucose metabolism in frontotemporal dementia: a longitudinal 18F-FDG-PET-study. Neurobiol. Aging 28, 42–50 (2007).

    CAS  PubMed  Google Scholar 

  104. 104

    Dickerson, B. C. & Sperling, R. A. Neuroimaging biomarkers for clinical trials of disease-modifying therapies in Alzheimer's disease. NeuroRx 2, 348–360 (2005).

    PubMed  PubMed Central  Google Scholar 

  105. 105

    Foster, N. L. et al. Realizing the potential of positron emission tomography with 18F-fluorodeoxyglucose to improve the treatment of Alzheimer's disease. Alzheimers Dement. 4 (Suppl. 1), S29–S36 (2008).

    PubMed  Google Scholar 

  106. 106

    Matthews, B., Siemers, E. R. & Mozley, P. D. Imaging-based measures of disease progression in clinical trials of disease-modifying drugs for Alzheimer disease. Am. J. Geriatr. Psychiatry 11, 146–159 (2003).

    PubMed  Google Scholar 

  107. 107

    Mega, M. S. et al. Cognitive and metabolic responses to metrifonate therapy in Alzheimer disease. Neuropsychiatry Neuropsychol. Behav. Neurol. 14, 63–68 (2001).

    CAS  PubMed  Google Scholar 

  108. 108

    Stefanova, E. et al. Longitudinal PET evaluation of cerebral glucose metabolism in rivastigmine treated patients with mild Alzheimer's disease. J. Neural Transm. 113, 205–218 (2006).

    CAS  PubMed  Google Scholar 

  109. 109

    Tune, L. et al. Donepezil HCl (E2020) maintains functional brain activity in patients with Alzheimer disease: results of a 24-week, double-blind, placebo-controlled study. Am. J. Geriatr. Psychiatry 11, 169–177 (2003).

    PubMed  Google Scholar 

  110. 110

    Mega, M. S. et al. Metabolic patterns associated with the clinical response to galantamine therapy: a fludeoxyglucose F 18 positron emission tomographic study. Arch. Neurol. 62, 721–728 (2005).

    PubMed  Google Scholar 

  111. 111

    Teipel, S. J. et al. Effects of donepezil on cortical metabolic response to activation during 18FDG-PET in Alzheimer's disease: a double-blind cross-over trial. Psychopharmacology (Berl.) 187, 86–94 (2006).

    CAS  Google Scholar 

  112. 112

    Kadir, A. et al. Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease. Ann. Neurol. 63, 621–631 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. 113

    Smith, G. S. et al. Cholinergic modulation of the cerebral metabolic response to citalopram in Alzheimer's disease. Brain 132, 392–401 (2009).

    PubMed  PubMed Central  Google Scholar 

  114. 114

    Tuszynski, M. H. et al. A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat. Med. 11, 551–555 (2005).

    CAS  Google Scholar 

  115. 115

    Eriksdotter Jonhagen, M. et al. Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 9, 246–257 (1998).

    CAS  PubMed  Google Scholar 

  116. 116

    Lahiri, D. K. et al. The experimental Alzheimer's disease drug posiphen[(+)-phenserine] lowers amyloid-β peptide levels in cell culture and mice. J. Pharmacol. Exp. Ther. 320, 386–396 (2007).

    CAS  PubMed  Google Scholar 

  117. 117

    Marutle, A. et al. Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine. Proc. Natl Acad. Sci. USA 104, 12506–12511 (2007).

    CAS  PubMed  Google Scholar 

  118. 118

    Razifar, P. et al. An automated method for delineating a reference region using masked volumewise principal-component analysis in 11C-PIB PET. J. Nucl. Med. Technol. 37, 38–44 (2009).

    PubMed  Google Scholar 

  119. 119

    Razifar, P., Ringheim, A., Engler, H., Hall, H. & Långström, B. Masked-volume-wise PCA and “reference Logan” illustrate similar regional differences in kinetic behavior in human brain PET study using [11C]-PIB. BMC Neurol. 9, 2 (2009).

    PubMed  PubMed Central  Google Scholar 

  120. 120

    Nordberg, A. Amyloid imaging in Alzheimer's disease. Curr. Opin. Neurol. 20, 398–402 (2007).

    CAS  PubMed  Google Scholar 

  121. 121

    Petersen, R. C. Mild cognitive impairment as a diagnostic entity. J. Intern. Med. 256, 183–194 (2004).

    CAS  PubMed  Google Scholar 

  122. 122

    Roivainen, A. et al. Biodistribution and blood metabolism of 1-11C-methyl-4-piperidinyl n-butyrate in humans: an imaging agent for in vivo assessment of butyrylcholinesterase activity with PET. J. Nucl. Med. 45, 2032–2039 (2004).

    CAS  PubMed  Google Scholar 

  123. 123

    Nelissen, N. et al. Phase 1 study of the Pittsburgh compound B derivative 18F-flutemetamol in healthy volunteers and patients with probable Alzheimer disease. J. Nucl. Med. 50, 1251–1259 (2009).

    CAS  PubMed  Google Scholar 

  124. 124

    Verhoeff, N. P. et al. In-vivo imaging of Alzheimer disease beta-amyloid with [11C]SB-13 PET. Am. J. Geriatr. Psychiatry 12, 584–595 (2004).

    PubMed  Google Scholar 

  125. 125

    Kudo, Y. et al. 2-(2-[2-Dimethylaminothiazol-5-yl]ethenyl)-6- (2-[fluoro]ethoxy)benzoxazole: a novel PET agent for in vivo detection of dense amyloid plaques in Alzheimer's disease patients. J. Nucl. Med. 48, 553–561 (2007).

    CAS  PubMed  Google Scholar 

  126. 126

    Choi, S. R. et al. Preclinical properties of 18F-AV-45: a PET agent for Aβ plaques in the brain. J. Nucl. Med. 50, 1887–1894 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. 127

    Nyberg, S. et al. Detection of amyloid in Alzheimer's disease with positron emission tomography using [11C]AZD2184. Eur. J. Nucl. Med. Mol. Imaging 36, 1859–1863 (2009).

    PubMed  PubMed Central  Google Scholar 

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A. Nordberg gratefully acknowledges the financial support provided by the following: the Swedish Research Council (project 05817), Stockholm County Council–Karolinska Institute (ALF grant), the Foundation for Old Servants, the Stohne's Foundation, the KI Foundations, the Alzheimer Foundation in Sweden, Swedish Brain Power, the EC-FP6 project DiMI (LSHB-CT-2005-512146 and QLK6-CT-2000-00502), and the Swedish Brain Foundation. Anton Forsberg, Michael Schöll (both Karolinska Institute) and Anders Wall (GE Healthcare, Uppsala, Sweden) are thanked for their help in preparing the figures.

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Nordberg, A., Rinne, J., Kadir, A. et al. The use of PET in Alzheimer disease. Nat Rev Neurol 6, 78–87 (2010).

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