Early diagnosis in Alzheimer's disease (AD), before the onset of marked clinical symptoms, is critical in preventing the irreversible neuronal damage that eventually leads to dementia and ultimately death. Therefore, there is an urgent need for in vivo imaging agents, which are valuable as specific biomarkers to demonstrate the location and density of amyloid plaques in the living human brain. The present manuscript describes a novel method for selective marking of A beta(40) fibrils by non-fluorescent gamma-Fe2O and fluorescent-magnetic gamma-Fe2O3-rhodamine or gamma-Fe2O3-Congo red nanoparticles, and the complete removal of the magnetized fibrils from the aqueous continuous phase by a magnetic field. These fluorescent-maghemite nanciparticles as multimodal imaging agents have a great advantage due to the combination of the magnetic and fluorescence imaging into one nanostructured system. This hybrid system, which selectively marks A beta(40) fibrils, might enable the early detection of plaques using both MRI and fluorescence microscopy, and therefore may be applied in in vivo AD diagnosis studies. These fluorescent-magnetic nanoparticles may also be useful as selective biomarkers to detect the location and the removal of other amyloid plaques derived from different amyloidogenic proteins that lead to neurodegenerative diseases, e.g., Parkinson's, Huntington's, mad cow, and prion diseases. (C) 2009 Elsevier Inc. All rights reserved.