Amyloid binding properties of curcumin analogues in Alzheimer’s disease postmortem brain tissue

• Published in: Neuroscience letters 2016-09, Vol.630, p.183-188
• Main Authors: Veldman, Emma R., Jia, Zhisheng, Halldin, Christer, Svedberg, Marie M.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - metabolism; Alzheimeŕs disease; Aminopyridines - pharmacology; Amyloid beta-Peptides - pharmacology; Autoradiography; Benzothiazoles - pharmacology; Curcumin; Curcumin - analogs & derivatives; Curcumin - pharmacology; Curcuminoid; Diarylheptanoids; Female; Human postmortem brain; Humans; Inhibitory Concentration 50; Male; Temporal Lobe - metabolism; β-amyloid
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2016.07.045

•Binding properties of curcuminoids to Aβ containing plaques in the AD postmortem tissue.•Bisdemethoxycurcumin might be a potential radioligand for Aβ plaque imaging.•[3H]Bisdemethoxycurcumin accumulation in all layers of cortical gray matter. The presence of β-amyloid (Aβ) containing plaques in the brain is a hallmark of Alzheimer’s disease (AD) and serves as a biomarker for confirmation of diagnosis postmortem. Early diagnosis is of great importance for optimal treatment and for monitoring disease progression in the brain. Highly specific and sensitive biomarkers are thus greatly needed to assess therapeutic efficacy, not only clinically, but also in terms of clearance of histopathological lesions and decelerated neurodegeneration. The objective of the present study was to give more insight into the binding of curcumin analogues, curcuminoids, to Aβ containing plaques in postmortem tissue from AD patients. In vitro autoradiography was utilized to explore affinity and displacement of the curcuminoids; curcumin, demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC) and dimethoxycurcumin (DIMC). We found that BDMC had the highest affinity for Aβ containing plaques in cortical AD brain tissue in comparison to other curcuminoids. Subsequently, [3H]BDMC showed significantly higher specific binding in cortical AD brain tissue compared to control subjects. These findings suggest that curcumin analogues, especially BDMC, may serve as a potential radioligands for Aβ plaque neuroimaging.