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 Cho; Bong Rae Cho; Bong Rae Cho

doi:10.1021/acschemneuro.0c00211

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

* Honorary professors

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

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 language	English
Pages (from-to)	1801-1810
Number of pages	10
Journal	ACS Chemical Neuroscience
Volume	11
Issue number	12
DOIs	https://doi.org/10.1021/acschemneuro.0c00211
Publication status	Published - 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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10.1021/acschemneuro.0c00211

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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

Choi, JW, Ju, YH, Ju, YH, Choi, Y, Choi, Y, Hyeon, SJ, Gadhe, CG, Park, JH, Kim, MS, Baek, S, Kim, Y, Park, KD, Park, KD, Pae, AN, Pae, AN, Ryu, H, Ryu, H, Lee, CJ, Lee, CJ, Cho, BR, Cho, BR & Cho, BR 2020, 'PyrPeg, a Blood-Brain-Barrier-Penetrating Two-Photon Imaging Probe, Selectively Detects Neuritic Plaques, Not Tau Aggregates', ACS Chemical Neuroscience, vol. 11, no. 12, pp. 1801-1810. https://doi.org/10.1021/acschemneuro.0c00211

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

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.",

keywords = "Alzheimer's disease, Tau protein, Two-photon imaging, blood-brain barrier-penetrating, neuritic plaques, α-synuclein",

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

note = "Funding Information: This research was supported by the Brain Research Program of the National Research Foundation (NRF) funded by the Ministry of Science and ICT (2018M3C7A1056682) and an NRF grant funded by the Korean government (NRF-2018R1A2B6006029). Publisher Copyright: Copyright {\textcopyright} 2020 American Chemical Society.",

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month = jun,

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doi = "10.1021/acschemneuro.0c00211",

language = "English",

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AU - Choi, Ji Woo

AU - Ju, Yeon Ha

AU - Choi, Yunsook

AU - Hyeon, Seung Jae

AU - Gadhe, Changdev G.

AU - Park, Jong Hyun

AU - Kim, Mun Seok

AU - Baek, Seungyeop

AU - Kim, Youngsoo

AU - Park, Ki Duk

AU - Pae, Ae Nim

AU - Ryu, Hoon

AU - Lee, C. Justin

AU - Cho, Bong Rae

N1 - Funding Information: This research was supported by the Brain Research Program of the National Research Foundation (NRF) funded by the Ministry of Science and ICT (2018M3C7A1056682) and an NRF grant funded by the Korean government (NRF-2018R1A2B6006029). Publisher Copyright: Copyright © 2020 American Chemical Society.

PY - 2020/6/17

Y1 - 2020/6/17

N2 - 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.

AB - 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.

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KW - Tau protein

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

Abstract

Keywords

ASJC Scopus subject areas

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