PyrPeg, a Blood-Brain-Barrier-Penetrating Two-Photon Imaging Probe, Selectively Detects Neuritic Plaques, Not Tau Aggregates

Ji Woo Choi, Yeon Ha Ju, Yeon Ha Ju, Yunsook Choi, Yunsook Choi, Seung Jae Hyeon, Changdev G. Gadhe, Jong Hyun Park, Mun Seok Kim, Seungyeop Baek, Youngsoo Kim, Ki Duk Park, Ki Duk Park, Ae Nim Pae, Ae Nim Pae, Hoon Ryu, Hoon Ryu, C. Justin Lee, C. Justin Lee, Bong Rae ChoBong Rae Cho, Bong Rae Cho

Research output: Contribution to journalArticle

Abstract

Amyloid-β (Aβ) tracers have made a significant contribution to the treatment of Alzheimer's disease (AD) by allowing a definitive diagnosis in living patients. Unfortunately, they also detect tau and other protein aggregates that compromise test accuracy. In AD research, there has been a growing need for in vivo Aβ imaging by two-photon microscopy, which enables deep-brain-fluorescence imaging. There is no suitable neuritic Aβ probe for two-photon microscopy. Here we report PyrPeg, a novel two-photon fluorescent probe that can selectively target insoluble Aβ rather than tau and α-synuclein aggregates in the AD model brain and postmortem brain. When injected intravenously, PyrPeg detects the neuritic plaques in the brain and olfactory bulb of the AD model. PyrPeg may serve as a useful blood-brain-barrier-penetrating diagnostic tool for optical and functional monitoring of insoluble forms of Aβ aggregates in the living AD brain.

Original languageEnglish
Pages (from-to)1801-1810
Number of pages10
JournalACS Chemical Neuroscience
Volume11
Issue number12
DOIs
Publication statusPublished - 2020 Jun 17

Keywords

  • Alzheimer's disease
  • Tau protein
  • Two-photon imaging
  • blood-brain barrier-penetrating
  • neuritic plaques
  • α-synuclein

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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  • Cite this

    Choi, J. W., Ju, Y. H., Ju, Y. H., Choi, Y., Choi, Y., Hyeon, S. J., Gadhe, C. G., Park, J. H., Kim, M. S., Baek, S., Kim, Y., Park, K. D., Park, K. D., Pae, A. N., Pae, A. N., Ryu, H., Ryu, H., Lee, C. J., Lee, C. J., ... Cho, B. R. (2020). PyrPeg, a Blood-Brain-Barrier-Penetrating Two-Photon Imaging Probe, Selectively Detects Neuritic Plaques, Not Tau Aggregates. ACS Chemical Neuroscience, 11(12), 1801-1810. https://doi.org/10.1021/acschemneuro.0c00211