BACKGROUND: Alzheimer's disease is characterized by two notorious protein aggregates in the brain: extracellular senile plaques mainly consisting of amyloid-β peptides and tau-protein-derived intracellular paired helical filaments. The diagnosis of Alzheimer's disease is impaired by insufficient sensitivity and specificity of diagnostic methods to visualize these pathological hallmarks over all disease stages. OBJECTIVE: The established fluorescence marker methoxy-X04 stains plaques, tau tangles and amyloid-derived angiopathies with good specificity, yet it is limited by slow elimination in vivo. Since the need for new markers is high, we prepared methoxy-X04 derivatives and evaluated their potential as imaging agents in Alzheimer's disease pathology. METHODS AND RESULTS: In this study, we describe an improved synthesis for methoxy-X04 and its derivatives and their affinity determination for the respective protein targets by immunohistology and a displacement assay. CONCLUSION: This resulted in the identification of new derivatives of methoxy-X04 with improved binding affinity.
BACKGROUND:Alzheimer's disease is characterized by two notorious protein aggregates in the brain: extracellular senile plaques mainly consisting of amyloid-β peptides and tau-protein-derived intracellular paired helical filaments. The diagnosis of Alzheimer's disease is impaired by insufficient sensitivity and specificity of diagnostic methods to visualize these pathological hallmarks over all disease stages. OBJECTIVE: The established fluorescence marker methoxy-X04 stains plaques, tau tangles and amyloid-derived angiopathies with good specificity, yet it is limited by slow elimination in vivo. Since the need for new markers is high, we prepared methoxy-X04 derivatives and evaluated their potential as imaging agents in Alzheimer's disease pathology. METHODS AND RESULTS: In this study, we describe an improved synthesis for methoxy-X04 and its derivatives and their affinity determination for the respective protein targets by immunohistology and a displacement assay. CONCLUSION: This resulted in the identification of new derivatives of methoxy-X04 with improved binding affinity.
Authors: Hannah Pellkofer; Friedrich Ihler; Bernhard G Weiss; Janina Trothe; Harindranath Kadavath; Monika Chongtham; Marcel Kunadt; Dietmar Riedel; Finn Lornsen; Petra Wilken; Claudia Bartels; Sina Hirschel; Sebastian G Russo; Elke Stransky; Lutz Trojan; Boris Schmidt; Eckhardt Mandelkow; Markus Zweckstetter; Martin Canis; Anja Schneider Journal: Eur Arch Psychiatry Clin Neurosci Date: 2018-11-12 Impact factor: 5.270
Authors: Julian M Carosi; Leanne K Hein; Mark van den Hurk; Robert Adams; Bridget Milky; Sanjna Singh; Cedric Bardy; Donna Denton; Sharad Kumar; Timothy J Sargeant Journal: Autophagy Date: 2020-09-22 Impact factor: 16.016
Authors: Nicole Schröder; Anja Schaffrath; Josua A Welter; Tim Putzka; Angelika Griep; Patrick Ziegler; Elisa Brandt; Sebastian Samer; Michael T Heneka; Hannes Kaddatz; Jiangshan Zhan; Eugenia Kipp; Thomas Pufe; Simone C Tauber; Markus Kipp; Lars-Ove Brandenburg Journal: J Neuroinflammation Date: 2020-04-24 Impact factor: 8.322