title: Identification of SPARC-like 1 protein as part of a biomarker panel for Alzheimer's disease in cerebrospinal fluid.
abstract: We have used proteomic fingerprinting to investigate diagnosis of Alzheimer's disease (AD). Samples of lumbar cerebrospinal fluid (CSF) from clinically-diagnosed AD cases (n = 33), age-matched controls (n = 20), and mild cognitive impairment (MCI) patients (n = 10) were used to obtain proteomic profiles, followed by bioinformatic analysis that generated a set of potential biomarkers in CSF samples that could discriminate AD cases from controls. The identity of the biomarker ions was determined using mass spectroscopy. The panel of seven peptide biomarker ions was able to discriminate AD patients from controls with a median accuracy of 95% (sensitivity 85%, specificity 97%). When this model was applied to an independent blind dataset from MCI patients, the intensity of signals was intermediate between the control and AD patients implying that these markers could potentially predict patients with early neurodegenerative disease. The panel were identified, in order of predictive ability, as SPARC-like 1 protein, fibrinogen alpha chain precursor, amyloid-β, apolipoprotein E precursor, serum albumin precursor, keratin type I cytoskeletal 9, and tetranectin. The 7 ion ANN model was further validated using an independent cohort of samples, where the model was able to classify AD cases from controls with median accuracy of 84.5% (sensitivity 93.3%, specificity 75.7%). Validation by immunoassay was performed on the top three identified markers using the discovery samples and an independent sample cohort which was from postmortem confirmed AD patients (n = 17).
authors: The John van Geest Cancer Research Centre, Nottingham Trent University, School of Science and Technology, Clifton Lane, Nottingham, UK.
authors: Baharak
authors: B
authors: Vafadar-Isfahani
authors: Graham
authors: G
authors: Ball
authors: Clare
authors: C
authors: Coveney
authors: Christophe
authors: C
authors: Lemetre
authors: David
authors: D
authors: Boocock
authors: Lennart
authors: L
authors: Minthon
authors: Oskar
authors: O
authors: Hansson
authors: Amanda Kathleen
authors: AK
authors: Miles
authors: Sabina M
authors: SM
authors: Janciauskiene
authors: Donald
authors: D
authors: Warden
authors: A David
authors: AD
authors: Smith
authors: Gordon
authors: G
authors: Wilcock
authors: Noor
authors: N
authors: Kalsheker
authors: Robert
authors: R
authors: Rees
authors: Balwir
authors: B
authors: Matharoo-Ball
authors: Kevin
authors: K
authors: Morgan
mesh_terms: D000465:Algorithms; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D019540:Area Under Curve; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002135:Calcium-Binding Proteins / Q000134:cerebrospinal fluid*; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis; D015331:Cohort Studies; D019295:Computational Biology; D003599:Cytoskeleton / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000134:cerebrospinal fluid*; D005260:Female; D005340:Fibrinogen / Q000134:cerebrospinal fluid; D006801:Humans; D008297:Male; D016571:Neural Networks, Computer; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010449:Peptide Mapping / Q000379:methods; D040901:Proteomics / Q000379:methods; D011569:Psychiatric Status Rating Scales; D012372:ROC Curve; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D010446:Peptide Fragments; C503126:SPARCL1 protein, human; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C464794:fibrinogen Aalpha; D016875:tau Proteins; D005340:Fibrinogen