Detection of a soluble form of BACE-1 in human cerebrospinal fluid by a sensitive activity assay

Clinical Chemistry
Jan H VerheijenRoeland Hanemaaijer

Abstract

Formation of deposits of the insoluble amyloid beta-peptide is believed to be causally related with neurodegeneration in Alzheimer disease (AD). The beta-peptide originates from a larger amyloid precursor protein (APP) by the action of proteolytic enzymes. The first proteolytic event leading to amyloid formation is the cleavage of APP by the membrane-bound aspartyl protease BACE-1, also known as memapsin-2. Inhibition of BACE-1 is thought to be a therapeutic approach to AD. Measuring BACE-1 activity in biological samples would be useful to elucidate the mechanism of AD and for development of AD drugs. We developed a sensitive and specific activity assay for BACE-1. The assay is based on a genetically engineered proenzyme that is specifically activated by BACE-1. The resulting active enzyme is measured with a chromogenic substrate. The use of 2 coupled reactions produces a detection limit as low as 0.4 pmol/L. The assay detected BACE-1 activity in extracts of human brain tissue as well as, unexpectedly, in human cerebrospinal fluid (CSF). Gel electrophoresis and Western blotting identified the BACE-1 present in CSF as a truncated soluble form of the originally membrane-bound BACE-1. Detection of the soluble form of BACE-1 in CSF...Continue Reading

References

May 16, 1984·Biochemical and Biophysical Research Communications·G G Glenner, C W Wong
Nov 24, 1999·Molecular and Cellular Neurosciences·I HussainG Christie
Dec 14, 2001·The Journal of Biological Chemistry·Fiona Grüninger-LeitchHeinz Döbeli
Dec 10, 2002·Neurobiology of Aging·Martin Citron
Feb 27, 2003·Journal of Neurochemistry·Alfredo G TomasselliRiqiang Yan
Jul 15, 2003·The Journal of Biological Chemistry·Ishrut HussainColin Dingwall
Oct 17, 2003·Journal of Medicinal Chemistry·Varghese JohnRobert L Heinrikson
Nov 19, 2003·Analytical Biochemistry·Myungsok OhWoo Jin Park
Apr 23, 2004·Trends in Pharmacological Sciences·Martin Citron
Jul 28, 2004·The American Journal of Pathology·Jan H N LindemanPancras C W Hogendoorn
Sep 29, 2004·The Biochemical Journal·Pablo Fuentes-Prior, Guy S Salvesen
May 25, 2005·International Journal of Experimental Pathology·Claus Pietrzik, Christian Behl
Jun 17, 2005·Analytical Biochemistry·Beth L PietrakMing-Tain Lai

❮ Previous
Next ❯

Citations

Aug 25, 2012·Biomarkers in Medicine·Anne M Fagan, Richard J Perrin
Jun 1, 2007·Biomarkers in Medicine·Ulf AndreassonHenrik Zetterberg
Feb 14, 2014·Trends in Molecular Medicine·Robert PerneczkyAlexander Kurz
Nov 17, 2007·Molecular Neurodegeneration·Sarah L Cole, Robert Vassar
Jul 1, 2009·The Journal of Biological Chemistry·David R TaylorNigel M Hooper
Jun 27, 2013·Molecular Neurodegeneration·Christoffer RosénHenrik Zetterberg
Feb 22, 2012·Neuromolecular Medicine·Christoffer RosénHenrik Zetterberg
Nov 13, 2012·Neurogenetics·R M Damian HolsingerPadraig Strappe
Oct 18, 2008·International Review of Psychiatry·Fernando Taragano
Oct 18, 2008·International Review of Psychiatry·Jeffrey L Cummings
Feb 10, 2009·Scandinavian Journal of Clinical and Laboratory Investigation·Henrik Zetterberg
Jul 9, 2008·Scandinavian Journal of Clinical and Laboratory Investigation·Harald Hampel, Yong Shen
Feb 3, 2016·Trends in Neurosciences·Soraia BarãoBart De Strooper
Jul 4, 2012·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Harald HampelZaven S Khachaturian
Sep 6, 2011·Journal of Neuroscience Methods·Amanda GonzalesMarwan N Sabbagh
Apr 29, 2011·Progress in Neurobiology·Bob OlssonKaj Blennow
Oct 10, 2009·Experimental Neurology·Harald HampelKaj Blennow
Oct 13, 2015·Journal of Proteomics·Angelo PalmigianoDomenico Garozzo
Mar 19, 2009·The FEBS Journal·Clare E Hunt, Anthony J Turner
Mar 25, 2011·Journal of Neuroscience Research·Guoxin WuMary J Savage
Nov 21, 2013·Acta Neuropathologica Communications·María-Salud García-AyllónJavier Sáez-Valero
Sep 18, 2015·Frontiers in Neurology·Aaron Ritter, Jeffrey Cummings
Sep 25, 2015·Journal of Alzheimer's Disease : JAD·Simone ListaHarald Hampel
Jul 22, 2015·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Ju-Hee KangUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Jun 18, 2015·Frontiers in Neurology·Inmaculada Lopez-FontJavier Sáez-Valero
Mar 21, 2015·Journal of Alzheimer's Disease : JAD·Mary J SavageUNKNOWN Foundation for National Institutes of Health (FNIH) Biomarkers Consortium CSF Proteomics Project Team for Alzheimer's Diseas
Jul 2, 2010·Nature Reviews. Drug Discovery·Harald HampelKaj Blennow
May 13, 2018·BMC Medical Genetics·Hao HuUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Oct 10, 2013·Clinical Pharmacology and Therapeutics·J Cummings, K Zhong
Jul 11, 2019·Molecular Neurobiology·Inmaculada Lopez-FontJavier Sáez-Valero
May 31, 2018·European Archives of Psychiatry and Clinical Neuroscience·Jessyka Maria de França BramOrestes Vicente Forlenza
Mar 16, 2013·Current Opinion in Psychiatry·Christoffer Rosén, Henrik Zetterberg
Nov 1, 2016·Personalized Medicine·Patricia Regina ManzineMárcia Regina Cominetti
Oct 18, 2020·Alzheimer's Research & Therapy·Harald HampelUNKNOWN Alzheimer’s Precision Medicine Initiative (APMI)

❮ Previous
Next ❯

Related Concepts

Related Feeds

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.

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.