title: Lumbar Cerebrospinal Fluid Biomarkers of Posthemorrhagic Hydrocephalus of Prematurity: Amyloid Precursor Protein, Soluble Amyloid Precursor Protein α, and L1 Cell Adhesion Molecule.
abstract: Intraventricular hemorrhage (IVH) is the most frequent, severe neurological complication of prematurity and is associated with posthemorrhagic hydrocephalus (PHH) in up to half of cases. PHH requires lifelong neurosurgical care and is associated with significant cognitive and psychomotor disability. Cerebrospinal fluid (CSF) biomarkers may provide both diagnostic information for PHH and novel insights into its pathophysiology.
  
  
  
  To explore the diagnostic ability of candidate CSF biomarkers for PHH.
  
  
  
  Concentrations of amyloid precursor protein (APP), soluble APPα (sAPPα), soluble APPβ, neural cell adhesion molecule-1 (NCAM-1), L1 cell adhesion molecule (L1CAM), tau, phosphorylated tau, and total protein (TP) were measured in lumbar CSF from neonates in 6 groups: (1) no known neurological disease (n = 33); (2) IVH grades I to II (n = 13); (3) IVH grades III to IV (n = 12); (4) PHH (n = 12); (5) ventricular enlargement without hydrocephalus (n = 10); and (6) hypoxic ischemic encephalopathy (n = 13). CSF protein levels were compared using analysis of variance, and logistic regression was performed to examine the predictive ability of each marker for PHH.
  
  
  
  Lumbar CSF levels of APP, sAPPα, L1CAM, and TP were selectively increased in PHH compared with all other conditions (all P < .001). The sensitivity, specificity, and odds ratios of candidate CSF biomarkers for PHH were determined for APP, sAPPα, and L1CAM; cut points of 699, 514, and 113 ng/mL yielded odds ratios for PHH of 80.0, 200.0, and 68.75, respectively.
  
  
  
  Lumbar CSF APP, sAPPα, L1CAM, and TP were selectively increased in PHH. These proteins, and sAPPα, in particular, hold promise as biomarkers of PHH and provide novel insight into PHH-associated neural injury and repair.
authors: Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors: Diego M
authors: DM
authors: Morales
authors: Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors: Shawgi A
authors: SA
authors: Silver
authors: Depart-ment of Neurological Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors: Clinton D
authors: CD
authors: Morgan
authors: Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors: Deanna
authors: D
authors: Mercer
authors: Department of Pediatrics, Harvard University School of Medicine, Boston, Massachusetts.
authors: Terri E
authors: TE
authors: Inder
authors: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri.|Hope Center for Neurological Disorders, Washington University School of Medi-cine, St. Louis, Missouri.|Knight Alzheimer's Disease Research Center, Washing-ton University School of Medicine, St. Louis, Missouri.
authors: David M
authors: DM
authors: Holtzman
authors: Division of Biostat-istics, Washington University School of Medicine, St. Louis, Missouri.
authors: Michael J
authors: MJ
authors: Wallendorf
authors: Depart-ment of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
authors: Rakesh
authors: R
authors: Rao
authors: Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors: James P
authors: JP
authors: McAllister
authors: Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri.|Hope Center for Neurological Disorders, Washington University School of Medi-cine, St. Louis, Missouri.|Depart-ment of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
authors: David D
authors: DD
authors: Limbrick
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002543:Cerebral Hemorrhage / Q000134:cerebrospinal fluid* / Q000150:complications; D005260:Female; D006801:Humans; D006849:Hydrocephalus / Q000134:cerebrospinal fluid*; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000134:cerebrospinal fluid*; D016015:Logistic Models; D008297:Male; D039842:Neural Cell Adhesion Molecule L1 / Q000134:cerebrospinal fluid*; D016017:Odds Ratio; D012680:Sensitivity and Specificity
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D039842:Neural Cell Adhesion Molecule L1
keywords: Amyloid precursor protein; Biomarker; Cerebrospinal fluid; Intraventricular hemorrhage; L1CAM; Neurosurgery; Posthemorrhagic hydrocephalus; Preterm; sAPPα