title: The Cerebrospinal Fluid Neurogranin/BACE1 Ratio is a Potential Correlate of Cognitive Decline in Alzheimer's Disease.
abstract: In diagnosing Alzheimer's disease (AD), ratios of cerebrospinal fluid (CSF) biomarkers, such as CSF Aβ1-42/tau, have an improved diagnostic performance compared to the single analytes, yet, still a limited value to predict cognitive decline. Since synaptic dysfunction/loss is closely linked to cognitive impairment, synaptic proteins are investigated as candidate CSF AD progression markers.
  
  
  
  We studied CSF levels of the postsynaptic protein neurogranin and protein BACE1, predominantly localized presynaptically, and their relation to CSF total-tau, Aβ1-42, Aβ1-40, and Aβ1-38. All six analytes were considered as single parameters as well as ratios.
  
  
  
  Every ELISA involved was based on monoclonal antibodies, including the BACE1 and neurogranin immunoassay. The latter specifically targets neurogranin C-terminally truncated at P75, a more abundant species of the protein in CSF. We studied patients with MCI due to AD (n = 38) and 50 dementia due to AD patients, as well as age-matched cognitively healthy elderly (n = 20). A significant subset of the patients was followed up by clinical and neuropsychological (MMSE) examinations for at least one year.
  
  
  
  The single analytes showed statistically significant differences between the clinical groups, but the ratios of analytes indeed had a higher diagnostic performance. Furthermore, only the ratio of CSF neurogranin trunc P75/BACE1 was significantly correlated with the yearly decline in MMSE scores in patients with MCI and dementia due to AD, pointing toward the prognostic value of the ratio.
  
  
  
  This is the first study demonstrating that the CSF neurogranin trunc P75/BACE1 ratio, reflecting postsynaptic/presynaptic integrity, is related to cognitive decline.
authors.affiliation: ADx NeuroSciences NV, Technologiepark Zwijnaarde 4, 9052 Gent, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: De Vos
authors.affiliation: Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Hanne
authors.initials: H
authors.lastname: Struyfs
authors.affiliation: ADx NeuroSciences NV, Technologiepark Zwijnaarde 4, 9052 Gent, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Jacobs
authors.affiliation: StatUa Center for Statistics, University of Antwerp, Antwerp, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Fransen
authors.affiliation: Department of Neuropathology, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Tom
authors.initials: T
authors.lastname: Klewansky
authors.affiliation: Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.|Developmental and Lifespan Psychology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: De Roeck
authors.affiliation: Neurodegenerative Brain Diseases Group, VIB Department of Molecular Genetics, Antwerp, Belgium.|Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Robberecht
authors.affiliation: Neurodegenerative Brain Diseases Group, VIB Department of Molecular Genetics, Antwerp, Belgium.|Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.affiliation: Department of Neuropathology, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.affiliation: 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.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Engelborghs
authors.affiliation: ADx NeuroSciences NV, Technologiepark Zwijnaarde 4, 9052 Gent, Belgium.
authors.forename: Eugeen
authors.initials: E
authors.lastname: Vanmechelen
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications*; D053829:Amyloid Precursor Protein Secretases / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D019540:Area Under Curve; D016282:Aspartic Acid Endopeptidases / Q000134:cerebrospinal fluid*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000209:etiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D051579:Neurogranin / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins; D051579:Neurogranin; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: Alzheimer’s disease; BACE1 protein; ELISA; biomarkers; cerebrospinal fluid; mild cognitive impairment; neurogranin; prognostic; ratio