title: COB231 targets amyloid plaques in post-mortem human brain tissue and  in an Alzheimer mouse model.
abstract: Previous works have shown the interest of naturally fluorescent proflavine derivatives to label Abeta deposits in vitro. This study aimed to further characterize the properties of the proflavine 3-acetylamino-6-[3-(propargylamino)propanoyl]aminoacridine (COB231) derivative as a probe. This compound was therefore evaluated on human post-mortem and mice brain slices and in vivo in 18-month-old triple transgenic mice APPswe, PS1M146V and tauP301L (3xTgAD) mice presenting the main characteristics of Alzheimer's disease (AD). COB231 labelled amyloid plaques on brain slices of AD patients, and 3xTgAD mice at 10 and 0.1 μM respectively. However, no labelling of the neurofibrillary tangle-rich areas was observed either at high concentration or in the brain of fronto-temporal dementia patients. The specificity of this mapping was attested in mice using Thioflavin S and IMPY as positive controls of amyloid deposits. After intravenous injection of COB231 in old 3xTgAD mice, fluorescent amyloid plaques were detected in the cortex and hippocampus, demonstrating COB231 blood–brain barrier permeability. We also controlled the cellular localization of COB231 on primary neuronal cultures and showed that COB231 accumulates into the cytoplasm and not into the nucleus. Finally, using a viability assay, we only detected a slight cytotoxic effect of COB231 (< 10%) for the highest concentration (100 μM).
authors.forename: Dominique
authors.initials: D
authors.lastname: Garin
authors.forename: Angélique
authors.initials: A
authors.lastname: Virgone-Carlotta
authors.forename: Bülent
authors.initials: B
authors.lastname: Gözel
authors.forename: Fatima
authors.initials: F
authors.lastname: Oukhatar
authors.forename: Pascale
authors.initials: P
authors.lastname: Perret
authors.forename: Danièle
authors.initials: D
authors.lastname: Marti-Battle
authors.forename: Monique
authors.initials: M
authors.lastname: Touret
authors.forename: Philippe
authors.initials: P
authors.lastname: Millet
authors.forename: Michel
authors.initials: M
authors.lastname: Dubois-Dauphin
authors.forename: David
authors.initials: D
authors.lastname: Meyronet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Streichenberger
authors.forename: Frank M
authors.initials: FM
authors.lastname: Laferla
authors.forename: Martine
authors.initials: M
authors.lastname: Demeunynck
authors.forename: Sabine
authors.initials: S
authors.lastname: Chierici
authors.forename: Marcelle
authors.initials: M
authors.lastname: Sallanon Moulin
authors.forename: Catherine
authors.initials: C
authors.lastname: Ghezzi
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000585:Aminacrine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D001344:Autopsy; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D058225:Plaque, Amyloid / Q000175:diagnosis*; D011370:Proflavine / Q000031:analogs & derivatives*; D012680:Sensitivity and Specificity; D013194:Staining and Labeling / Q000379:methods
chemical_list: C000609669:3-acetylamino-6-(3-(propargylamino)propanoyl)aminoacridine; D005456:Fluorescent Dyes; D000585:Aminacrine; D011370:Proflavine