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.
|Number of pages||3|
|Journal||Bioorganic and Medicinal Chemistry Letters|
|State||Published - Dec 1 2014|
Bibliographical noteFunding 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.
© 2014 Elsevier Ltd. All rights reserved.
- Alzheimer's disease
- Detection of amyloid fibrils
- Tritium-labeled probe
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry