Tritium-labeled (E,E)-2,5-bis(4′-hydroxy-3′-carboxystyryl)benzene as a probe for β-amyloid fibrils

Sergey V. Matveev; Stefan Kwiatkowski; Vitaliy M. Sviripa; Robert C. Fazio; David S. Watt; Harry Levine

doi:10.1016/j.bmcl.2014.09.075

Tritium-labeled (E,E)-2,5-bis(4′-hydroxy-3′-carboxystyryl)benzene as a probe for β-amyloid fibrils

Sergey V. Matveev, Stefan Kwiatkowski, Vitaliy M. Sviripa, Robert C. Fazio, David S. Watt, Harry Levine

Molecular and Cellular Biochemistry

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

4 Scopus citations

Abstract

Accumulation of Aβ in the brains of Alzheimer disease (AD) patients reflects an imbalance between Aβ production and clearance from their brains. Alternative cleavage of amyloid precursor protein (APP) by processing proteases generates soluble APP fragments including the neurotoxic amyloid Aβ40 and Aβ42 peptides that assemble into fibrils and form plaques. Plaque-buildup occurs over an extended time-frame, and the early detection and modulation of plaque formation are areas of active research. Radiolabeled probes for the detection of amyloid plaques and fibrils in living subjects are important for noninvasive evaluation of AD diagnosis, progression, and differentiation of AD from other neurodegenerative diseases and age-related cognitive decline. Tritium-labeled (E,E)-1-[³H]-2,5-bis(4′-hydroxy-3′-carbomethoxystyryl)benzene possesses an improved level of chemical stability relative to a previously reported radioiodinated analog for radiometric quantification of Aβ plaque and tau pathology in brain tissue and in vitro studies with synthetic Aβ and tau fibrils.

Original language	English
Pages (from-to)	5534-5536
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	23
DOIs	https://doi.org/10.1016/j.bmcl.2014.09.075
State	Published - Dec 1 2014

Bibliographical note

Funding Information:
H.L. was supported by the Coins for Alzheimer’s Research Trust (C.A.R.T.) of the Rotary Clubs of North Carolina, South Carolina, and Georgia; the National Institute of Neurological Disorders and Stroke ( R21 NS080576 ); an unrestricted ‘Grants4Targets’ Grant from Bayer Healthcare ; and a University of Kentucky Research Support Grant. D.S.W. was supported by the Office of the Dean of the College of Medicine and by NIH Grant Number P20 RR020171 from the National Institute of General Medical Sciences to L. Hersh, P.I. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, the NINDS, or the NIGMS.

Publisher Copyright:
© 2014 Elsevier Ltd. All rights reserved.

Keywords

Alzheimer's disease
Detection of amyloid fibrils
Tritium-labeled probe
β-Amyloid

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2014.09.075

Cite this

@article{141b092923da4c83a8c0f056dea4fb5b,

title = "Tritium-labeled (E,E)-2,5-bis(4′-hydroxy-3′-carboxystyryl)benzene as a probe for β-amyloid fibrils",

abstract = "Accumulation of Aβ in the brains of Alzheimer disease (AD) patients reflects an imbalance between Aβ production and clearance from their brains. Alternative cleavage of amyloid precursor protein (APP) by processing proteases generates soluble APP fragments including the neurotoxic amyloid Aβ40 and Aβ42 peptides that assemble into fibrils and form plaques. Plaque-buildup occurs over an extended time-frame, and the early detection and modulation of plaque formation are areas of active research. Radiolabeled probes for the detection of amyloid plaques and fibrils in living subjects are important for noninvasive evaluation of AD diagnosis, progression, and differentiation of AD from other neurodegenerative diseases and age-related cognitive decline. Tritium-labeled (E,E)-1-[3H]-2,5-bis(4′-hydroxy-3′-carbomethoxystyryl)benzene possesses an improved level of chemical stability relative to a previously reported radioiodinated analog for radiometric quantification of Aβ plaque and tau pathology in brain tissue and in vitro studies with synthetic Aβ and tau fibrils.",

keywords = "Alzheimer's disease, Detection of amyloid fibrils, Tritium-labeled probe, β-Amyloid",

author = "Matveev, {Sergey V.} and Stefan Kwiatkowski and Sviripa, {Vitaliy M.} and Fazio, {Robert C.} and Watt, {David S.} and Harry Levine",

note = "Funding Information: H.L. was supported by the Coins for Alzheimer{\textquoteright}s Research Trust (C.A.R.T.) of the Rotary Clubs of North Carolina, South Carolina, and Georgia; the National Institute of Neurological Disorders and Stroke ( R21 NS080576 ); an unrestricted {\textquoteleft}Grants4Targets{\textquoteright} Grant from Bayer Healthcare ; and a University of Kentucky Research Support Grant. D.S.W. was supported by the Office of the Dean of the College of Medicine and by NIH Grant Number P20 RR020171 from the National Institute of General Medical Sciences to L. Hersh, P.I. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, the NINDS, or the NIGMS. Publisher Copyright: {\textcopyright} 2014 Elsevier Ltd. All rights reserved.",

year = "2014",

month = dec,

day = "1",

doi = "10.1016/j.bmcl.2014.09.075",

language = "English",

volume = "24",

pages = "5534--5536",

number = "23",

}

TY - JOUR

T1 - Tritium-labeled (E,E)-2,5-bis(4′-hydroxy-3′-carboxystyryl)benzene as a probe for β-amyloid fibrils

AU - Matveev, Sergey V.

AU - Kwiatkowski, Stefan

AU - Sviripa, Vitaliy M.

AU - Fazio, Robert C.

AU - Watt, David S.

AU - Levine, Harry

N1 - Funding Information: H.L. was supported by the Coins for Alzheimer’s Research Trust (C.A.R.T.) of the Rotary Clubs of North Carolina, South Carolina, and Georgia; the National Institute of Neurological Disorders and Stroke ( R21 NS080576 ); an unrestricted ‘Grants4Targets’ Grant from Bayer Healthcare ; and a University of Kentucky Research Support Grant. D.S.W. was supported by the Office of the Dean of the College of Medicine and by NIH Grant Number P20 RR020171 from the National Institute of General Medical Sciences to L. Hersh, P.I. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, the NINDS, or the NIGMS. Publisher Copyright: © 2014 Elsevier Ltd. All rights reserved.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Accumulation of Aβ in the brains of Alzheimer disease (AD) patients reflects an imbalance between Aβ production and clearance from their brains. Alternative cleavage of amyloid precursor protein (APP) by processing proteases generates soluble APP fragments including the neurotoxic amyloid Aβ40 and Aβ42 peptides that assemble into fibrils and form plaques. Plaque-buildup occurs over an extended time-frame, and the early detection and modulation of plaque formation are areas of active research. Radiolabeled probes for the detection of amyloid plaques and fibrils in living subjects are important for noninvasive evaluation of AD diagnosis, progression, and differentiation of AD from other neurodegenerative diseases and age-related cognitive decline. Tritium-labeled (E,E)-1-[3H]-2,5-bis(4′-hydroxy-3′-carbomethoxystyryl)benzene possesses an improved level of chemical stability relative to a previously reported radioiodinated analog for radiometric quantification of Aβ plaque and tau pathology in brain tissue and in vitro studies with synthetic Aβ and tau fibrils.

AB - Accumulation of Aβ in the brains of Alzheimer disease (AD) patients reflects an imbalance between Aβ production and clearance from their brains. Alternative cleavage of amyloid precursor protein (APP) by processing proteases generates soluble APP fragments including the neurotoxic amyloid Aβ40 and Aβ42 peptides that assemble into fibrils and form plaques. Plaque-buildup occurs over an extended time-frame, and the early detection and modulation of plaque formation are areas of active research. Radiolabeled probes for the detection of amyloid plaques and fibrils in living subjects are important for noninvasive evaluation of AD diagnosis, progression, and differentiation of AD from other neurodegenerative diseases and age-related cognitive decline. Tritium-labeled (E,E)-1-[3H]-2,5-bis(4′-hydroxy-3′-carbomethoxystyryl)benzene possesses an improved level of chemical stability relative to a previously reported radioiodinated analog for radiometric quantification of Aβ plaque and tau pathology in brain tissue and in vitro studies with synthetic Aβ and tau fibrils.

KW - Alzheimer's disease

KW - Detection of amyloid fibrils

KW - Tritium-labeled probe

KW - β-Amyloid

UR - http://www.scopus.com/inward/record.url?scp=84910107592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84910107592&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2014.09.075

DO - 10.1016/j.bmcl.2014.09.075

M3 - Article

C2 - 25452000

AN - SCOPUS:84910107592

SN - 0960-894X

VL - 24

SP - 5534

EP - 5536

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 23

ER -

Tritium-labeled (E,E)-2,5-bis(4′-hydroxy-3′-carboxystyryl)benzene as a probe for β-amyloid fibrils

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this