Close Correlation of Monoamine Oxidase Activity with Progress of Alzheimer’s Disease in Mice, Observed by in Vivo Two-Photon Imaging

Abstract

Monoamine oxidases (MAOs) play an important role in Alzheimer’s disease (AD) pathology. We report in vivo comonitoring of MAO activity and amyloid-β (Aβ) plaques dependent on the aging of live mice with AD, using a two-photon fluorescence probe. The probe under the catalytic action of MAO produces a dipolar fluorophore that senses Aβ plaques, a general AD biomarker, enabling us to comonitor the enzyme activity and the progress of AD indicated by Aβ plaques. The results show that the progress of AD has a close correlation with MAO activity, which can be categorized into three stages: slow initiation stage up to three months, an aggressive stage, and a saturation stage from nine months. Histological analysis also reveals elevation of MAO activity around Aβ plaques in aged mice. The close correlation between the MAO activity and AD progress observed by in vivo monitoring for the first time prompts us to investigate the enzyme as a potential biomarker of AD.

Harnessing Intramolecular Rotation To Enhance Two‐photon Imaging of Aβ Plaques through Minimizing Background Fluorescence

“…In this work, we describe a new fluorophore, named intramolecular rotation‐enabled iminocoumarin 1 (IRI‐1), to overcome some of the drawbacks of the previously described fluorophores. We sought to combine the excellent characteristics of other dyes selective for Aβ protein aggregates, namely the large two‐photon cross‐section of coumarin‐based dyes such as IBC‐2, the large signal‐to‐background ratios of ThT, and emission reaching into the near‐infrared (NIR, >650 nm). In ThT, the large increase in fluorescence intensity upon binding the target protein is conferred by the presence of an efficient de‐excitation pathway mediated by the molecular rotor principle .…”

Monitoring of Monoamine Oxidases as Biomarkers of Disease and Disorder

“…In 2016, Ahn and co‐workers reported a close correlation between the upregulated MAO‐B activity and the progress of AD by in vivo comonitoring of fluorescence intensity at the amyloid‐beta plaques, which is the biomarker of AD and background signal of brain . MAO probe 1 is converted to IBC 2 fluorophore by the MAO‐induced enzymatic reaction and cascade intramolecular cyclization with fluorescence recovery (Figure ).…”

Rational Design of a Two‐Photon Fluorogenic Probe for Visualizing Monoamine Oxidase A Activity in Human Glioma Tissues

“…[8] To date,M AO TPFPs have been mainly designed to detect either MAO-B or both isoforms of MAOs. [9] ForM AO-A-specific detection, however,o nly OPFPs have been reported thus far, including three reactionand one binding-based probes ( Figure 1A). [10] Ma and coworkers first reported an ovel MAO-A specific OPFP ( AC probe)f or visualizing MAO-A activity in live cells based on as ubstrate-oxidized enzymatic reaction.…”