Functional bioprobe for responsive imaging and inhibition of amyloid-β oligomer based on curcuminoid scaffold

Alzheimer's Disease (AD) is a type of neural disease, which is characterized by behavioural disorder and progressive loss of cognitive function. Since there are no obvious symptoms of early-stage AD, it is difficult to differentiate AD with other types of dementia. Therefore, early diagnosis of AD is particularly important. Previous studies have shown that Aβ oligomer is present earlier in patients' brains; it is also more toxic than Aβ fibril. However, there are few Aβ oligomer-specific bioprobes reported. We herein report a functional probe which responds to and inhibits Aβ oligomer formation. It uses a pyrimidine moiety as an acceptor group, N, N-dimethylaniline as the donor, and together with the binding group build a “donor-acceptor-donor (D-A-D)” conjugated scaffold. The structure-activity relationship was analysed and predicted with molecular docking to explore the binding mode, which is π-π stacking and H-bonding between the probe and Aβ oligomer. The stability, selectivity and responsibility of the probe were studied, and its toxicity was examined through MTT assay. In vitro and in vivo studies indicated that the probe could target the Aβ oligomer and rapidly penetrate the blood-brain barrier to reach the hippocampus region. This study explores the potential of the newly designed bioprobe for the early diagnosis of Alzheimer's disease. • Amphiphilic NIRF bioprobe based on curcuminoid scaffold were designed and synthesized ( JP-1 and JP-2 ). • The responsive imaging and inhibition towards amyloid-β oligomer were summarized. • Both in vitro and in vivo studies have discussed the potential of JP-1 and JP-2 as early diagnosis of Alzheimer's disease.