Ann De Vos1, Dirk Jacobs1, Hanne Struyfs2, Erik Fransen3, Kerstin Andersson4, Erik Portelius4, Ulf Andreasson4, Didier De Surgeloose5, Daniëlle Hernalsteen5, Kristel Sleegers6, Caroline Robberecht6, Christine Van Broeckhoven6, Henrik Zetterberg7, Kaj Blennow4, Sebastiaan Engelborghs8, Eugeen Vanmechelen9. 1. Department of Research, ADx NeuroSciences, Ghent, Belgium. 2. Department of Biomedical Sciences, Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. 3. Department of Biomedical Sciences, StatUa Center for Statistics, University of Antwerp, Antwerp, Belgium. 4. Department of Psychiatry and Neurochemistry, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Gothenburg University, Mölndal, Sweden. 5. Department of Radiology, Hospital Network Antwerp (ZNA) Middelheim, Antwerp, Belgium. 6. Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Department of Molecular Genetics, Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. 7. Department of Psychiatry and Neurochemistry, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Gothenburg University, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. 8. Department of Biomedical Sciences, Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium. 9. Department of Research, ADx NeuroSciences, Ghent, Belgium. Electronic address: eugeen.vanmechelen@adxneurosciences.com.
Abstract
INTRODUCTION: Biomarkers monitoring synaptic degeneration/loss would be valuable for Alzheimer's disease (AD) diagnosis. Postsynaptic protein neurogranin may be a promising cerebrospinal fluid (CSF) biomarker but has not yet been evaluated as a plasma biomarker. METHODS: Using an in-house designed prototype enzyme-linked immunosorbent assay (ELISA) targeting neurogranin C-terminally, we studied neurogranin in paired CSF/plasma samples of controls (n = 29) versus patients experiencing MCI, or dementia, due to AD (in total n = 59). RESULTS: CSF neurogranin was increased in AD and positively correlated with CSF tau, whereas there was a negative relationship between CSF neurogranin (and tau) and CSF Aβ1-42/Aβ1-40. No differences were detected in plasma neurogranin between controls and AD. Also, there was no correlation between CSF and plasma neurogranin, excluding confounding effects of the latter. DISCUSSION: This study strengthens the potential of neurogranin as an AD CSF biomarker, which now needs validation in larger studies. As tools, straightforward immunoassays can be used, as demonstrated by the described ELISA.
INTRODUCTION: Biomarkers monitoring synaptic degeneration/loss would be valuable for Alzheimer's disease (AD) diagnosis. Postsynaptic protein neurogranin may be a promising cerebrospinal fluid (CSF) biomarker but has not yet been evaluated as a plasma biomarker. METHODS: Using an in-house designed prototype enzyme-linked immunosorbent assay (ELISA) targeting neurogranin C-terminally, we studied neurogranin in paired CSF/plasma samples of controls (n = 29) versus patients experiencing MCI, or dementia, due to AD (in total n = 59). RESULTS: CSF neurogranin was increased in AD and positively correlated with CSF tau, whereas there was a negative relationship between CSF neurogranin (and tau) and CSF Aβ1-42/Aβ1-40. No differences were detected in plasma neurogranin between controls and AD. Also, there was no correlation between CSF and plasma neurogranin, excluding confounding effects of the latter. DISCUSSION: This study strengthens the potential of neurogranin as an AD CSF biomarker, which now needs validation in larger studies. As tools, straightforward immunoassays can be used, as demonstrated by the described ELISA.
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