A quadrupolar two-photon fluorescent probe for in vivo imaging of amyloid-? plaques.

ABSTRACT: The formation of beta amyloid (A?) plaques in specific brain regions is one of the early pathological hallmarks of Alzheimer's disease (AD). To enable the early detection of AD and related applications, a method for real-time, clear 3D visualization of A? plaques in vivo is highly desirable. Two-photon microscopy (TPM) which utilizes two near-infrared photons is an attractive tool for such applications. However, this technique needs a sensitive and photostable two-photon (TP) probe possessing bright TP exited fluorescence to impart high signal-to-noise (S/N) visualization of A? plaques. Herein, we report a quadrupolar TP fluorescent probe (QAD1) having large TP action cross section (??_max = 420 GM) and its application for in vivo TPM imaging of A? plaques. This probe, designed with a centrosymmetric D-A-D motif with a cyclic conjugating bridge and solubilizing unit, displays bright TP excited fluorescence, appreciable water solubility, robust photostability, and high sensitivity and selectivity for A? plaques. Using the real-time TPM imaging of transgenic 5XFAD mice after intravenous injection of QAD1, we show that this probe readily enters the blood brain barrier and provides high S/N ratio images of individual A? plaques in vivo. We also used QAD1 in dual-color TPM imaging for 3D visualization of A? plaques along with blood vessels and cerebral amyloid angiopathy (CAA) inside living mouse brains. These findings demonstrate that this probe will be useful in biomedical applications including early diagnosis and treatments of AD.

SUBMITTER: Heo CH 

PROVIDER: S-EPMC6016450 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature