Accumulation of
amyloid-beta (Aβ) into
amyloid plaques and hyperphosphorylated tau into neurofibrillary tangles (NFTs) are pathological hallmarks of
Alzheimer's disease (AD). There is a significant intra- and inter-individual variability in the morphology and conformation of Aβ aggregates, which may account in part for the extensive clinical and pathophysiological heterogeneity observed in AD. In this study, we sought to identify an array of
fluorescent dyes to specifically probe Aβ aggregates, in an effort to address their diversity. We screened a small library of
fluorescent probes and identified three
benzothiazole-coumarin derivatives that stained both vascular and parenchymal Aβ deposits in AD brain sections. The set of these three
dyes allowed the visualization of Aβ deposits in three different colors (blue, green and far-red). Importantly, two of these
dyes specifically stained Aβ deposits with no apparent staining of hyperphosphorylated tau or α-
synuclein deposits. Furthermore, this set of
dyes demonstrated differential interactions with distinct types of Aβ deposits present in the same subject. Aβ aggregate-specific
dyes identified in this study have the potential to be further developed into Aβ imaging probes for the diagnosis of AD. In addition, the far-red
dye we identified in this study may serve as an imaging probe for small animal imaging of Aβ pathology. Finally, these
dyes in combination may help us advance our understanding of the relation between the various Aβ deposits and the clinical diversity observed in AD.