Antibody-Based In Vivo PET Imaging Detects Amyloid-β Reduction in Alzheimer Transgenic Mice After BACE-1 Inhibition

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Silvio R MeierDag Sehlin

Abstract

Visualization of amyloid-β (Aβ) pathology with PET has become an important tool for making a specific clinical diagnosis of Alzheimer disease (AD). However, the available amyloid PET radioligands, such as 11C-Pittsburgh compound B, reflect levels of insoluble Aβ plaques but do not capture soluble and protofibrillar Aβ forms. Furthermore, the plaque load appears to be fairly static during clinical stages of AD and may not be affected by Aβ-reducing treatments. The aim of the present study was to investigate whether a novel PET radioligand based on an antibody directed toward soluble aggregates of Aβ can be used to detect changes in Aβ levels during disease progression and after treatment with a β-secretase (BACE-1) inhibitor. Methods: One set of transgenic mice (tg-ArcSwe, a model of Aβ pathology) aged between 7 and 16 mo underwent PET with the Aβ protofibril-selective radioligand 124I-RmAb158-scFv8D3 (where RmAb is recombinant mouse monoclonal antibody and scFv is single-chain variable fragment) to follow progression of Aβ pathology in the brain. A second set of tg-ArcSwe mice, aged 10 mo, were treated with the BACE-1 inhibitor NB-360 for 3 mo and compared with an untreated control group. A third set of tg-ArcSwe mice, also age...Continue Reading

References

Apr 10, 1992·Science·J A Hardy, G A Higgins
Oct 1, 1963·The Biochemical Journal·F C GREENWOODJ S GLOVER
Dec 3, 2003·Molecular Imaging·Andreas Markus Loening, Sanjiv Sam Gambhir
Jul 21, 2006·Brain : a Journal of Neurology·Henry EnglerAgneta Nordberg
Feb 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Robert M KoffieTara L Spires-Jones
Dec 12, 2012·Annals of Neurology·Thomas J EsparzaDavid L Brody
Jun 20, 2013·Journal of Alzheimer's Disease : JAD·Kristina MagnussonLars N G Nilsson
Feb 20, 2016·Nature Communications·Dag SehlinStina Syvänen
Sep 2, 2016·Nature·Jeff SevignyAlfred Sandrock
Dec 6, 2016·Scientific Reports·Thomas J EsparzaDavid L Brody
Jun 15, 2017·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Steven DeleyeSteven Staelens
Jul 20, 2017·Journal of Biomedical Science·Shih-Ya Hung, Wen-Mei Fu
Jul 26, 2017·Proceedings of the National Academy of Sciences of the United States of America·Aylin D KeskinMarc Aurel Busche

❮ Previous
Next ❯

Citations

Mar 19, 2020·International Journal of Molecular Sciences·Christopher D MorroneJoAnne McLaurin
Aug 12, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dag SehlinStina Syvänen
Jul 26, 2019·European Journal of Nuclear Medicine and Molecular Imaging·Dag SehlinUNKNOWN MINC faculty
Sep 29, 2019·Journal of Alzheimer's Disease : JAD·Marlena ZyśkAnna Erlandsson
Aug 4, 2019·Progress in Neurobiology·Kasper Bendix JohnsenTorben Moos
Feb 24, 2021·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Silvio R MeierStina Syvänen
May 20, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Wejdan M ArifGert Luurtsema
May 1, 2021·International Journal of Molecular Sciences·Yiyun JinFrancesco Antonio Aprile
Jul 16, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Christian SacherMatthias Brendel
Jun 4, 2021·Fluids and Barriers of the CNS·Rebecca FaresjöStina Syvänen
Nov 26, 2020·ACS Chemical Neuroscience·Stina SyvänenDag Sehlin
Oct 16, 2020·Fluids and Barriers of the CNS·Y WoutersM Dewilde
Jun 6, 2021·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Silvio R MeierStina Syvänen

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
transgenic

Software Mentioned

Zen
Photoshop CC
GraphPad
Prism
Amide

Related Concepts

Related Feeds

Alzheimer's Disease: Neuroimaging

Neuroimaging can help identify pathological hallmarks of Alzheimer's disease (AD). Here is the latest research on neuroimaging modalities, including magnetic resonance imaging and positron emission tomography, in AD.

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.