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Neuropathological correlates of dopaminergic imaging in Alzheimer's disease and Lewy body dementias

Lookup NU author(s): Dr Sean Colloby, Shane McParland, Professor John O'Brien, Professor Johannes Attems

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Abstract

Investigation of dopaminergic transporter loss in vivo using (123)I-N-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl) nortropane single photon emission computed tomography has been widely used as a diagnostic aid in Lewy body disease. However, it is not clear whether the pathological basis for the imaging changes observed reflects loss of dopaminergic transporter expressing neurons because of cell death or dysfunctional neurons due to possible nigral and/or striatal neurodegenerative pathology. We aimed to investigate the influence of nigral neuronal loss as well as nigral (alpha-synuclein, tau) and striatal (alpha-synuclein, tau, amyloid beta) pathology on striatal uptake in a cohort of autopsy-confirmed Alzheimer's disease (n = 4), dementia with Lewy bodies (n = 7) and Parkinson's disease dementia (n = 12) cases. Subjects underwent ante-mortem dopaminergic scanning and post-mortem assessments (mean interval 3.7 years). Striatal binding (caudate, anterior and posterior putamen) was estimated using region of interest procedures while quantitative neuropathological measurements of alpha-synuclein, tau and amyloid beta were carried out. Similarly, nigral neuronal density was assessed quantitatively. Stepwise linear regression was performed to identify significant pathological predictors of striatal binding. In all striatal regions, image uptake was associated with nigral dopaminergic neuronal density (P </= 0.04) but not alpha-synuclein (P >/= 0.46), tau (P >/= 0.18) or amyloid beta (P >/= 0.22) burden. The results suggest that reduced uptake in vivo may be influenced considerably by neuronal loss rather than the presence of pathological lesions, in particular those related to Alzheimer's disease and Lewy body dementias. However, dysfunctional nigral neurons may have an additional effect on striatal uptake in vivo but their respective role remains to be elucidated.


Publication metadata

Author(s): Colloby SJ, McParland S, O'Brien JT, Attems J

Publication type: Article

Journal: Brain

Year: 2012

Volume: 135

Issue: 9

Pages: 2798-808

ISSN (print): 0006-8950

ISSN (electronic): 1460-2156

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/brain/aws211

DOI: 10.1093/brain/aws211


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