Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-21T17:06:59.488Z Has data issue: false hasContentIssue false
  • English
  • Français

Amyloid imaging

Published online by Cambridge University Press:  10 June 2011

Victor L. Villemagne  and
Christopher C. Rowe
Victor L. Villemagne*
Affiliation:
Department of Nuclear Medicine and Centre for PET, Austin Health, Victoria, Australia Department of Medicine, Austin Health, Victoria, Australia The Mental Health Research Institute of Victoria, Victoria, Australia
Christopher C. Rowe
Affiliation:
Department of Nuclear Medicine and Centre for PET, Austin Health, Victoria, Australia Department of Medicine, Austin Health, Victoria, Australia
*
Correspondence should be addressed to: Victor L. Villemagne, MD, Austin Health, Department of Nuclear Medicine and Centre for PET, 145 Studley Rd, Heidelberg, VIC, 3084, Australia. Phone: +61 3-9496-3321; Fax: +61 3-9458-5663. Email: villemagne@petnm.unimelb.edu.au.
Get access

Abstract

Molecular neuroimaging techniques such as PET are proving valuable in the early and differential diagnosis of Alzheimer's disease (AD). With the advent of new therapeutic strategies aimed at reducing β-amyloid (Aβ) burden in the brain to potentially prevent or delay functional and irreversible cognitive loss, there is increased interest in developing agents that allow assessment of Aβ burden in vivo.

Amyloid imaging with PET has proven useful in the discrimination of dementias, showing significantly higher Aβ burden in the gray matter of AD patients when compared with healthy controls or patients with frontotemporal dementia. ApoE ɛ4 carriers, independent of diagnosis or disease severity, present with higher Aβ burden than non-ɛ4 carriers. Amyloid imaging matches histopathological reports in aging and dementia, reflecting the true regional density of Aβ plaques in cortical areas. It also appears to be more sensitive than FDG-PET for the diagnosis of AD.

In healthy older people there is an increasing prevalence of amyloid positive scans with age, rising from 20% in the seventh decade to 60% in the ninth decade. Of people with mild cognitive impairment (MCI), 40–60% present with detectable cortical Aβ deposition. In both groups, Aβ deposition is associated with a higher risk for cognitive decline and dementia due to AD. These observations suggest that Aβ deposition is not part of normal aging, supporting the hypothesis that it occurs well before the onset of symptoms and is likely to represent preclinical AD in asymptomatic persons and prodromal AD in MCI. Further longitudinal observations, coupled with different disease-specific tracers and biomarkers, are required to confirm this hypothesis and further elucidate the precise role of Aβ deposition in the course of AD.

Keywords

Alzheimer's diseaseAβdementiabrain imagingpositron emission tomography
Type
Review Article
Information
International Psychogeriatrics , Volume 23 , Supplement S2: Clinical use of neuroimaging in dementia: an international perspective , September 2011 , pp. S41 - S49
Copyright
Copyright © International Psychogeriatric Association 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aizenstein, H. J. et al. (2008). Frequent amyloid deposition without significant cognitive impairment among the elderly. Archives of Neurology, 65, 1509–1517.CrossRefGoogle ScholarPubMed
Braak, H. and Braak, E. (1997). Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiology of Aging, 18, 351–357.CrossRefGoogle ScholarPubMed
Chang, C. Y. and Silverman, D. H. (2004). Accuracy of early diagnosis and its impact on the management and course of Alzheimer's disease. Expert Reviews in Molecular Diagnosis, 4, 63–69.CrossRefGoogle ScholarPubMed
Chetelat, G. et al. (2010). Relationship between atrophy and beta-amyloid deposition in Alzheimer disease. Annals of Neurology 67, 317–324.CrossRefGoogle ScholarPubMed
Clark, C. M. et al. (2008). Biomarkers for early detection of Alzheimer pathology. Neurosignals, 16, 11–18.CrossRefGoogle ScholarPubMed
Clark, C. M. et al. (2011). Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA, 305, 275–283.CrossRefGoogle ScholarPubMed
Edison, P. et al. (2008). Amyloid load in Parkinson's disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography. Journal of Neurology, Neurosurgery and Psychiatry, 79, 1331–1338.CrossRefGoogle ScholarPubMed
Ellis, K. A. et al. (2009). The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer's disease. International Psychogeriatrics, 21, 672–687.CrossRefGoogle ScholarPubMed
Fagan, A. M. et al. (2006). Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta(42) in humans. Annals of Neurology, 59, 512–519.CrossRefGoogle ScholarPubMed
Fodero-Tavoletti, M. T. et al. (2011). [18F]-THK523, a novel in vivo tau imaging ligand for Alzheimer's disease. Brain, 134, 1089–1100.Google ScholarPubMed
Ikonomovic, M. D. et al. (2008). Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain, 131, 1630–1645.CrossRefGoogle Scholar
JackC. R., Jr. C. R., Jr. et al. (2010). Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurology, 9, 119–128.CrossRefGoogle ScholarPubMed
Johansson, A. et al. (2008). [(11)C]-PIB imaging in patients with Parkinson's disease: preliminary results. Parkinsonism and Related Disorders, 14, 345–347.CrossRefGoogle ScholarPubMed
Johnson, K. A. et al. (2007). Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Annals of Neurology, 62, 229–234.CrossRefGoogle ScholarPubMed
Jureus, A. et al. (2010). Characterization of AZD4694, a novel fluorinated Abeta plaque neuroimaging PET radioligand. Journal of Neurochemistry, 114, 784–794.CrossRefGoogle ScholarPubMed
Klunk, W. E. et al. (2004). Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Annals of Neurology, 55, 306–319.CrossRefGoogle ScholarPubMed
Klunk, W. E. et al. (2007). Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees. Journal of Neuroscience, 27, 6174–6184.CrossRefGoogle ScholarPubMed
Masters, C. L. et al. (2006). Molecular mechanisms for Alzheimer's disease: implications for neuroimaging and therapeutics. Journal of Neurochemistry, 97, 1700–1725.CrossRefGoogle ScholarPubMed
Mathis, C. A. et al. (2002). A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain. Bioorganic Medical Chemistry Letters, 12, 295–298.CrossRefGoogle ScholarPubMed
McKhann, G. et al. (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology, 34, 939–944.CrossRefGoogle ScholarPubMed
Morris, J. C. and Price, A. L. (2001). Pathologic correlates of nondemented aging, mild cognitive impairment, and early-stage Alzheimer's disease. Journal of Molecular Neuroscience, 17, 101–118.CrossRefGoogle ScholarPubMed
Morris, J. C. et al. (2010). APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Annals of Neurology, 67, 122–131.CrossRefGoogle Scholar
Ng, S. et al. (2007a). Visual assessment versus quantitative assessment of 11C-PIB PET and 18F-FDG PET for detection of Alzheimer's disease. Journal of Nuclear Medicine, 48, 547–552.CrossRefGoogle ScholarPubMed
Ng, S. Y. et al. (2007b). Evaluating atypical dementia syndromes using positron emission tomography with carbon 11 labeled Pittsburgh Compound B. Archives of Neurology, 64, 1140–1144.CrossRefGoogle ScholarPubMed
Ong, K. et al. (2010). Assessment of Aβ deposition in mild cognitive impairment with 18F-florbetaben. Alzheimer's and Dementia, 6, S26.CrossRefGoogle Scholar
Petersen, R. C. (2007). Mild cognitive impairment: current research and clinical implications. Seminars in Neurology, 27, 22–31.CrossRefGoogle ScholarPubMed
Pike, K. E. et al. (2007). Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. Brain, 130, 2837–2844.Google ScholarPubMed
Rabinovici, G. D. et al. (2007). 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology, 68, 1205–1212.CrossRefGoogle ScholarPubMed
Reiman, E. M. et al. (2009). Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America, 106, 6820–6825.CrossRefGoogle ScholarPubMed
Rowe, C. C. et al. (2007). Imaging beta-amyloid burden in aging and dementia. Neurology, 68, 1718–1725.CrossRefGoogle ScholarPubMed
Rowe, C. C. et al. (2008). Imaging of amyloid beta in Alzheimer's disease with (18)F-BAY94–9172, a novel PET tracer: proof of mechanism. Lancet Neurology, 7, 129–135.CrossRefGoogle ScholarPubMed
Rowe, C. C. et al. (2010). Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiology of Aging, 31, 1275–1283.CrossRefGoogle ScholarPubMed
Sabri, O. et al. (2010). Florbetaben for beta-amyloid brain PET in Alzheimer's disease: results of a multicenter phase 2 trial. Alzheimer's and Dementia, 6, S70.CrossRefGoogle Scholar
Senda, M. et al. (2010). Inter-ethnic comparability of pharmacokinetics of tlorbetaben (BAY 94–9172), a beta-amyloid imaging PET agent, as a basis of global development of a diagnostics for Alzheimer's disease. Alzheimer's and Dementia, 6, S48.CrossRefGoogle Scholar
Shaw, L. M. et al. (2007). Biomarkers of neurodegeneration for diagnosis and monitoring therapeutics. Nature Review of Drug Discoveries, 6, 295–303.CrossRefGoogle ScholarPubMed
Shoghi-Jadid, K. et al. (2002). Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. American Journal of Geriatric Psychiatry, 10, 24–35.CrossRefGoogle ScholarPubMed
Smith, E. E. et al. (2008). Magnetic resonance imaging white matter hyperintensities and brain volume in the prediction of mild cognitive impairment and dementia. Archives of Neurology, 65, 94–100.CrossRefGoogle ScholarPubMed
Sperling, R. et al. (2009). PET imaging of beta-amyloid with florpiramine F18 (18F-AV-45): preliminary results from a phase II study of cognitively normal elderly subjects, individuals with mild cognitive impairment, and patients with a clinical diagnosis of Alzheimer's disease. Alzheimer's and Dementia, 5, P197 [abstract].CrossRefGoogle Scholar
Tolboom, N. et al. (2009). Detection of Alzheimer pathology in vivo using both 11C-PIB and 18F-FDDNP PET. Journal of Nuclear Medicine, 50, 191–197.CrossRefGoogle ScholarPubMed
Vandenberghe, R. et al. (2010). 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial. Annals of Neurology, 68, 319–329.CrossRefGoogle ScholarPubMed
Villemagne, V. L. and Rowe, C. C. (2010). Amyloid ligands for dementia. PET Clinics, 5, 33–53.CrossRefGoogle ScholarPubMed
Villemagne, V. L. et al. (2006). The Abeta centric pathway of Alzheimer's disease. In Barrow, C. J. and Small, B. J. (eds.), Abeta Peptide and Alzheimer's Disease (pp. 5–32). London: Springer-Verlag.Google Scholar
Villemagne, V. L. et al. (2008a). Abeta deposits in older non-demented individuals with cognitive decline are indicative of preclinical Alzheimer's disease. Neuropsychologia, 46, 1688–1697.CrossRefGoogle ScholarPubMed
Villemagne, V. L. et al. (2008b). The ART of loss: Abeta imaging in the evaluation of Alzheimer's disease and other dementias. Molecular Neurobiology, 38, 1–15.CrossRefGoogle ScholarPubMed
Villemagne, V. L. et al. (2009a). High striatal amyloid beta-peptide deposition across different autosomal Alzheimer disease mutation types. Archives of Neurology, 66, 1537–1544.CrossRefGoogle ScholarPubMed
Villemagne, V. L. et al. (2009b). 11C-PiB PET studies in typical sporadic Creutzfeldt-Jakob disease. Journal of Neurology, Neurosurgery and Psychiatry, 80, 998–1001.CrossRefGoogle ScholarPubMed
Villemagne, V. L. et al. (2010). 18F-Florbetaben-PET imaging in the differential diagnosis of dementia. Alzheimer's and Dementia, 6, S70–S71.CrossRefGoogle Scholar
Villemagne, V. L. et al. (2011). Longitudinal assessment of Abeta and cognition in aging and Alzheimer disease. Annals of Neurology, 69, 181–192.CrossRefGoogle ScholarPubMed
Wong, D. F. et al. (2010). In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18). Journal of Nuclear Medicine, 51, 913–920.CrossRefGoogle Scholar