Dual-ligand fluorescence microscopy enables chronological and spatial histological assignment of distinct amyloid-β deposits.

Different types of deposits comprised of amyloid-b (Ab) peptides are one of the pathological hallmarks of Alzheimer's disease (AD) and novel methods that enable identification of a diversity of Ab deposits during the AD continuum are essential for understanding the role of these aggregates during the pathogenesis. Herein, different combinations of five fluorescent thiophene-based ligands were used for detection of Ab deposits in brain tissue sections from transgenic mouse models with aggregated Ab pathology, as well as brain tissue sections from patients affected by sporadic or dominantly inherited AD. When analyzing the sections with fluorescence microscopy, distinct ligand staining patterns related to the transgenic mouse model or to the age of the mice were observed. Likewise, specific staining patterns of different Ab deposits were revealed for sporadic versus dominantly inherited AD, as well as for distinct brain regions in sporadic AD. Thus, by using dualstaining protocols with multiple combinations of fluorescent ligands, a chronological and spatial histological designation of different Ab deposits could be achieved. This study demonstrates the potential of our approach for resolving the role and presence of distinct Ab aggregates during the AD continuum and pinpoints the necessity of using multiple ligands to obtain an accurate assignment of different Ab deposits in the neuropathological evaluation of AD, as well as when evaluating therapeutic strategies targeting Ab aggregates. [ABSTRACT FROM AUTHOR]