Neuroimaging for Lewy body disease: Is the in vivo molecular imaging of alpha-synuclein neuropathology required and feasible?

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Alpha-synuclein aggregation is a neuropathological hallmark of many neurodegenerative diseases including Parkinson's disease (PD), Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB), collectively termed the alpha-synucleinopathies. Substantial advances in clinical criteria and neuroimaging technology over the last 20 years have allowed great strides in the detection and differential diagnosis of these disorders. Nevertheless, it is clear that whilst the array of different imaging modalities in clinical use allow for a robust diagnosis of alpha-synucleinopathy in comparison to healthy subjects, there is no clear diagnostic imaging marker that affords a reliable differential diagnosis between the different forms of Lewy body disease (LBD) or that could facilitate tracking of disease progression. This has led to a call for a biomarker based on the pathological hallmarks of these diseases, namely alpha-synuclein-positive Lewy bodies (LBs). This potentially may be advantageous in terms of early disease detection, but may also be leveraged into a potential marker of disease progression. We here aim to firstly review the current status of neuroimaging biomarkers in PD and related synucleinopathies. Secondly, we outline the rationale behind alpha-synuclein imaging as a potential novel biomarker as well as the potential benefits and limitations of this approach. Thirdly, we attempt to illustrate the likely technical hurdles to be overcome to permit successful in vivo imaging of alpha-synuclein pathology in the diseased brain. Our overriding aim is to provide a framework for discussion of how to address this major unmet clinical need. (C) 2010 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)28 - 55
Number of pages28
JournalBrain Research Reviews
Issue number1
Publication statusPublished - Oct 2010


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