Iterative Design of Near-Infrared Fluorescent Probes for Early Diagnosis of Alzheimer’s Disease by Targeting Aβ Oligomers

Authors:
Publisher website
Google Scholar
Abstract
Amyloid-β oligomers (AβOs), crucial toxic proteins in early Alzheimer's disease (AD), precede the formation of Aβ plaques and cognitive impairment. In this context, we present our iterative process for developing novel near-infrared fluorescent (NIRF) probes specifically targeting AβOs, aimed at early AD diagnosis. An initial screening identified compound 18 as being highly selective for AβOs. Subsequent analysis revealed that compound 20 improved serum stability while retaining affinity for AβOs. The most promising iteration, compound 37, demonstrated exceptional qualities: a high affinity for AβOs, emission in the near-infrared region, and good biocompatibility. Significantly, ex vivo double staining indicated that compound 37 detected AβOs in AD mouse brain and in vivo imaging experiments showed that compound 37 could differentiate between 4-month-old AD mice and age-matched wild-type mice. Therefore, compound 37 has emerged as a valuable NIRF probe for early detection of AD and a useful tool in exploring AD's pathological mechanisms.
Funding Information
  • Jiangsu Provincial Key Research and Development Program (BE2020695)
  • Natural Science Foundation of Jiangsu Province (BK20191320)

This publication has 57 references indexed in Scilit: