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Amyloid Imaging in Alzheimer’s Disease and Other Dementias

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Abstract

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. Molecular neuroimaging techniques such as positron emission tomography (PET), in conjunction with related biomarkers in plasma and cerebrospinal fluid, are proving valuable in the early and differential diagnosis of Alzheimer’s disease (AD). 11C-PiB PET has proven useful in the discrimination of dementias, showing significantly higher PiB retention in grey matter of AD patients when compared with healthy controls or patients with frontotemporal dementia. 11C-PiB PET also appears to be more accurate than FDG for the diagnosis of AD. Despite apparently underestimating the Aβ burden in the brain, 11C-PiB PET is an optimal method to differentiate healthy controls from AD, matching histopathological reports in aging and dementia and reflecting the true regional density of Aβ plaques in cortical areas. High striatal Aβ deposition seems to be typical for carriers of familial forms of AD, whilst ApoE ε4 carriers, independent of diagnosis or disease severity, present with higher Aβ burden than non- ε4 carriers. Characterization of the binding properties of PiB has shown that despite binding to other misfolded proteins in vitro, PiB is extremely selective for Aβ at the concentrations achieved during a PET scan. Aβ burden as assessed by PET does not correlate with measures of cognition or cognitive decline in AD. Approximately 30% of apparently healthy older people, and 50–60% of people with mild cognitive impairment, present with cortical 11C-PiB retention. In these groups, Aβ burden does correlate with episodic memory and rate of memory decline. These observations suggest that Aβ deposition is not part of normal ageing, supporting the hypothesis that Αβ deposition occurs well before the onset of symptoms and is likely to represent preclinical AD. Further longitudinal observations, coupled with different disease-specific tracers and biomarkers are required not only to confirm this hypothesis, but also to better elucidate the role of Αβ deposition in the course of Alzheimer’s disease.

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Acknowledgements

This work was supported in part by the National Health and Medical Research Council of Australia, the Austin Hospital Medical Research Foundation, and Neurosciences Victoria.

We thank Henri Tochon-Danguy, Graeme O’Keefe, Uwe Ackermann, Rachel Mulligan, Jessica Sagona, Kunthi Pathmaraj, Tim Saunder, Jason Bradley, and Gareth Jones for their crucial role during radiochemical synthesis, PET examinations and image processing; Qiao-Xin Li and Katrina Laughton for ELISA processing; Laura Leone and Barbara Przybylowski for human brain tissue preparation; and Fairlie Hinton and Geoff Pavey from the National Neural Tissue Resource Centre for sourcing of human brain tissue.

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Authors and Affiliations

  1. Department of Pathology, The University of Melbourne, Melbourne, Victoria, 3010, Australia

    Michelle T. Fodero-Tavoletti, Roberto Cappai, Tiffany Cowie, Andrea R. Connor & Victor L. Villemagne

  2. Bio21 Molecular and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, 3010, Australia

    Michelle T. Fodero-Tavoletti, Roberto Cappai & Andrea R. Connor

  3. The Mental Health Research Institute of Victoria, Parkville, Victoria, 3052, Australia

    Michelle T. Fodero-Tavoletti, Roberto Cappai, Kerryn E. Pike, Paul A. Adlard, Andrea R. Connor, Colin L. Masters & Victor L. Villemagne

  4. Department of Anatomical Pathology, Alfred Hospital, Prahran, Victoria, 3181, Australia

    Catriona A. McLean

  5. Centre for PET, Austin Hospital, 145 Studley Rd, Heidelberg, Victoria, 3084, Australia

    Kerryn E. Pike, Christopher C. Rowe & Victor L. Villemagne

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  1. Michelle T. Fodero-Tavoletti
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  2. Roberto Cappai
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  10. Victor L. Villemagne
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Correspondence to Victor L. Villemagne.

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Fodero-Tavoletti, M.T., Cappai, R., McLean, C.A. et al. Amyloid Imaging in Alzheimer’s Disease and Other Dementias. Brain Imaging and Behavior 3, 246–261 (2009). https://doi.org/10.1007/s11682-009-9067-2

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