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The ART of Loss: Aβ Imaging in the Evaluation of Alzheimer’s Disease and other Dementias

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Abstract

Molecular neuroimaging based on annihilation radiation tomographic (ART) techniques such as positron emission tomography (PET), in conjunction with related biomarkers in plasma and cerebrospinal fluid (CSF), 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. Aβ burden as assessed by molecular imaging matches histopathological reports of Aβ plaque distribution in aging and dementia and appears more accurate than FDG for the diagnosis of AD. Aβ imaging is also a very powerful tool in the differential diagnosis of AD from fronto-temporal dementia (FTD). Although Aβ burden as assessed by PET does not correlate with measures of cognitive decline in AD, it does correlate with memory impairment and rate of memory decline in mild cognitive impairment (MCI) and healthy older subjects. Approximately 30% of asymptomatic controls present cortical 11C-PiB retention. These observations suggest that Aβ deposition is not part of normal ageing, supporting the hypothesis that Aβ deposition occurs well before the onset of symptoms and is likely to represent preclinical AD. Further longitudinal observations are required to confirm this hypothesis and to better elucidate the role of Aβ deposition in the course of Alzheimer’s disease.

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Acknowledgements

Supported in part by funds from the NHMRC Grant #509166, Austin Hospital Medical Research Foundation, Neurosciences Victoria, and the University of Melbourne.

We thank Prof. Michael Woodward, Dr Gaeme O’Keefe, Dr Henri Tochon-Danguy, Dr Catriona McLean, Dr Paul Adlard, Dr Gordon Chan, Dr Uwe Ackermann, Dr Rachel Mulligan, Dr Kenneth Young, Dr Sylvia Gong, Dr Greg Savage, Dr Paul Maruff, Dr David Darby, Dr William Browne, Dr Steven Ng, Ms Tiffany Cowie, Mr Tim Saunder, Ms Laura Leone, Ms Lisa Foster, Ms Clare Smith, Mr Gareth Jones, Mrs Fairlie Hinton, Ms Jessica Sagona, Mrs Kunthi Pathmaraj, Ms Bridget Chappell, Mr Jason Bradley, for their crucial role in our ongoing research projects.

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Villemagne, V.L., Fodero-Tavoletti, M.T., Pike, K.E. et al. The ART of Loss: Aβ Imaging in the Evaluation of Alzheimer’s Disease and other Dementias. Mol Neurobiol 38, 1–15 (2008). https://doi.org/10.1007/s12035-008-8019-y

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