With
increase of social aging, Alzheimer's disease (AD) has been one of the serious
diseases threatening human health. The occurrence of A<i>β </i>fibrils<i> </i>or
plaques is recognized as the hallmark of AD.<i> </i>Currently, optical imaging has
stood out to be a promising technique for the imaging of A<i>β</i> fibrils/plaques
and the diagnosis of AD. However, restricted by their poor blood-brain barrier (BBB)
penetrability, short-wavelength excitation and emission, and aggregation-caused
quenching (ACQ) effect, the clinically used gold-standard optical probes such
as <a>thioflavin</a> T (ThT) and thioflavin S (ThS), are not effective
enough in the early diagnosis of AD <i>in vivo</i>. Herein, we put forward an
“all-in-one” design principle and demonstrate its feasibility in developing
high-performance fluorescent probes which are specific to A<i>β</i> fibrils/plaques
and promising for super-early <i>in</i>-<i>vivo</i> diagnosis of AD. As a proof
of concept, a simple rod-like amphiphilic NIR fluorescent AIEgen, i.e., AIE-CNPy-AD,
is developed by taking the specificity, BBB penetration ability, deep-tissue
penetration capacity, high signal-to-noise ratio (SNR) into consideration. AIE-CNPy-AD
is constituted by connecting the electron-donating and accepting moieties through
single bonds and tagging with a propanesulfonate tail, giving rise to the NIR
fluorescence, aggregation-induced emission (AIE) effect, amphiphilicity, and rod-like
structure, which in turn result in high binding-affinity and excellent
specificity to A<i>β</i> fibrils/plaques, satisfactory ability to penetrate BBB
and deep tissues, ultrahigh SNR and sensitivity, and high-fidelity imaging
capability. <i>In-vitro, ex-vivo,</i> and
<i>in-vivo</i> <a>identifying of A<i>β</i> fibrils/plaques</a>
in different strains of mice indicate that AIE-CNPy-AD holds the universality
to the detection of A<i>β</i> fibrils/plaques. It is noteworthy that AIE-CNPy-AD is even able to trace the small and sparsely
distributed A<i>β</i> fibrils/plaques in very young
AD model mice such as 4-month-old APP/PS1 mice which are reported to be the youngest
mice to have A<i>β</i> deposits in brains, suggesting
its great potential in diagnosis and intervention of AD at a super-early stage.
Rationally Designing Simple Rod-Like Amphiphilic NIR-Emissive AIE Probes for Precise In-Vivo Detection of Aβ Fibrils/Plaques at A Super-Early Stage