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Amyloid-β oligomers (AβO) have been identified as core biomarkers for early diagnosis of Alzheimer's disease (AD). For the first time, a "turn-on" unlabeled colorimetric aptasensor based on aptamer-polythymine (polyT)-polyadenine (polyA)-gold nanoparticles (pA-pT-apt@AuNPs) was developed for highly sensitive and specific detection of amyloid-β 1-40 oligomers (Aβ40-O). In this system, polyA sequence could preferentially anchor onto AuNPs surface as well as reduce the non-specific adsorption, and the aptamer could form upright conformation for the specific recognition of Aβ40-O. The aggregation of pA-pT-apt@AuNPs was induced by MgCl 2. However, the addition of Aβ40-O enabled the aptamer fold adaptively upon recognition and aptamer-Aβ40-O complex formed surrounding AuNPs, effectively stabilizing pA-pT-apt@AuNPs against salt-induced aggregation, therefore the color of pA-pT-apt@AuNPs solution still retained red. Based on this principle, the proposed aptasensor exhibited high sensitivity with the limit of detection of 3.03 nM and a linear detectable range from 10.00 nM to 100.0 nM. The superb sensitivity was achieved via the optimization of the length of polyA and polyT spacer. This pA-pT-apt@AuNPs based colorimetric aptasensor provides a rapid, cost-effective, highly sensitive detection method for Aβ40-O, which is valuable for the early diagnosis of AD. [Display omitted] • A pA-pT-apt@AuNPs-based colorimetric aptasensor was developed for Aβ40-O detection. • The proposed aptasensor avoided the non-specific adsorption on AuNPs surface. • The upright conformation of aptamers benefited the specific recognition of Aβ40-O. • Superb sensitivity was achieved with the limit of detection of 3.03 nM. • The aptasensor is simple, rapid (response time of 1.5 h) and cost-effective. [ABSTRACT FROM AUTHOR]

Tau aggregation correlates rigorously with the progression and severity of Alzheimer's disease (AD). However, it is extremely challenging to develop tau-selective imaging probes due to similar β-sheet structures shared with Aβ fibrils. Herein, three new donor-π-acceptor fluorophores (T1 - T3) composed of 3,5-dimethoxy-N,N-dimethylaniline-4-yl and quinoxaline, bridged by 1–3 C C bond are rationally designed for selectively imaging tau aggregates. For the first time, we demonstrated the side substitution on D-π-A skeleton is significant for improving the selectivity of tau probes. Molecular docking results revealed that the lateral methoxy groups on molecular rotors could act as antennas to interact with surrounding tau hydrophilic residues via hydrogen-bond and other kinds of intermolecular interactions, improving selective recognition for tau aggregates. Compared with its non-side-substitution precursor T02 , T2 exhibited 4.7 times higher tau-over-Aβ selectivity after introducing methoxy substituents. Owing to the improved selectivity, T2 was successfully applied to detect tau aggregates in cells and pathologically relevant regions of AD mice model. This work verifies the pivotal role of side substitution on D-π-A skeleton in increasing the selectivity of tau probes, which provides a rational strategy to design novel tau probes with high selectivity in future. • An innovative strategy to improve selective imaging of tau aggregates was suggested. • Three new compounds T1-T3 synthesized and characterized accordingly. • Introducing lateral substituents improved tau-over-Aβ selectivity (4.7 times). • Probe T2 performed well in intracellular tau aggregates imaging and tissue staining. • The pivotal role of lateral substituents was revealed by molecular docking. [ABSTRACT FROM AUTHOR]